Vitamin B is a collective term for a group of water-soluble essential nutrients that play a crucial role in various metabolic pathways. These vitamins act as precursors of essential cofactors required for numerous biochemical processes. A deficiency in vitamin B can lead to a range of health issues, including cognitive dysfunction, neuropathy, cardiovascular disease (CVD), and osteoporosis. Unlike some nutrients, humans cannot synthesize vitamin B de novo, making dietary intake and synthesis by gut microbiota critical for maintaining adequate levels of these vitamins.

The Role of Gut Microbiota in Vitamin B Utilization

The gut microbiota, a diverse community of microorganisms residing in the human digestive tract, plays a significant role in the utilization of vitamin B. Gut bacteria are categorized into vitamin B-producers, which can synthesize and supply these vitamins to the host, and vitamin B-consumers, which require an external source of vitamin B to maintain their physiological functions. The balance between these two groups influences whether the gut microbiota acts as a supplier or competitor for vitamin B.

Several factors, including digestive enzymes, gut motility, gastrointestinal acidity, transporters, and bound proteins, influence the absorption of vitamin B. These factors are affected by various conditions, such as inflammatory bowel diseases (IBD), which can disrupt the absorption process. Pathogenic microbiota can trigger IBD, whereas probiotics can help normalize gut physiology, potentially improving vitamin B absorption.

Here’s a detailed table summarizing the information about all types of Vitamin B:

Vitamin Type	Forms	Roles	Deficiency Effects	Daily Intake	Sources	Absorption Mechanism	Microbiota Interaction	Impact on Health via Microbiota
Vitamin B1	Thiamine monochloride, Thiamine chloride, Aneurine	Cofactor in carbohydrate metabolism, glycolysis, tricarboxylic acid cycle	Cognitive dysfunction, neuropathy, cardiovascular disease (CVD), osteoporosis, drowsiness, beriberi, polyneuritis, Wernicke-Korsakoff syndrome	1.1–1.2 mg	Dietary, gut microbiota	Absorbed in small intestine (dietary), absorbed in large intestine (microbiota), relies on digestive enzymes, gut motility, acidity, transporters	Produced by Bacteroidetes, Fusobacteria, Prevotella, Actinobacteria, Clostridium; affects thiamine uptake and gut pH	Influences gut microbiota composition, SCFAs production; affects thiamine-dependent bacteria growth
Vitamin B2	Riboflavin	Precursor of FMN and FAD, energy metabolism, antioxidant, anti-inflammatory	Night blindness, cataracts, anemia, migraines, dermatological symptoms	1.3–1.7 mg	Dairy products, green vegetables, fruits, eggs, meat	Hydrolyzed by alkaline phosphatases and FMN/FAD pyrophosphatases, absorbed in small intestine, carrier-mediated process	Produced by Bacteroidetes, Fusobacteria, Proteobacteria; influenced by gastric emptying rate, gastric diseases	Affects growth of B. coccoides, R. intestinalis, E. faecalis; influences SCFAs production, gut microbiota diversity
Vitamin B3	Nicotinamide (NAM), Nicotinic Acid (NA)	Cofactor in cellular biochemistry and energy metabolism, antioxidant	Pellagra (inflammation, skin lesions, diarrhea, dementia), linked to glaucoma, lipid disorders	5–30 μg	Endogenous (tryptophan), exogenous (dietary NAM and NA)	Absorbed in stomach and upper small intestine, pH-dependent carrier-mediated mechanism, passive diffusion at high concentrations	Synthesized by B. fragilis, Prevotella copri, Ruminococcus lactaris, C. difficile, Bifidobacterium infantis; absorption influenced by lactic acid bacteria	Reduces intestinal inflammation, regulates antimicrobial peptide production, affects SCFAs production
Vitamin B6	Pyridoxine (PN), Pyridoxal, Pyridoxamine	Cofactor in amino acid metabolism, sphingolipid and carbohydrate metabolism	Neuromuscular irritability, peripheral neuropathy, dermatitis, stomatitis, cheilosis, immune system depression, sideroblastic anemia	1.3–1.7 mg	Animal products (PLP, PMP), plant products (PNP)	Hydrolyzed by pyridoxal phosphatase, absorbed by passive diffusion and carrier-mediated system, pH-dependent and amiloride-sensitive	Produced by B. fragilis, P. copri, B. longum, C. aerofaciens, H. pylori; affected by drugs, alcohol, smoking, gut motility, pH	Maintains gut microbiota profile, influences arginine biosynthesis, de novo protein synthesis, cell functions
Vitamin B7	Biotin	Cofactor for carboxylases in fatty acid, glucose, and amino acid metabolism	Skin abnormalities, neurological disturbances, growth retardation, inflammation, loss of appetite, glossitis, dandruff dermatitis, hair loss	35 μg for infants, 150–300 μg for adults	Dietary sources, bacterial synthesis in large intestine	Absorbed in proximal intestine, mediated by SMVT, bacterial synthesis absorbed in large intestine	Produced by B. fragilis, F. varium, C. coli; absorbed in jejunum, influenced by lactic acid bacteria, intestinal infections, high-fat diet	Influences gut microbiota abundance, particularly Prevotella, Bifidobacteria, Ruminococcus, Lactobacillus; affects SCFAs production
Vitamin B9	Folate	Cofactor in one-carbon metabolism, DNA and RNA biosynthesis, amino acid metabolism	Megaloblastic anemia, neural tube defects, associated with CVD, cancers, Alzheimer’s disease	400 μg	Fortified foods, supplements, pharmaceuticals	Hydrolyzed to monoglutamate form by glutamate carboxypeptidase II, absorbed in proximal jejunum, transported by PCFT, undergoes enterohepatic circulation	Produced by Actinobacteria, Proteobacteria, Fusobacteria, Firmicutes; absorbed in colon, influenced by gut microbiota diversity and composition	Increases gut microbiota richness and diversity, affects SCFAs production, influences Actinobacteria and Clostridia abundance
Vitamin B12	Cobalamin	Required by methionine synthase and methylmalonyl-CoA mutase, involved in methylation and mitochondrial metabolism	Increased tHcy levels (risk of CVD), cognitive impairment, neurological disorders, osteoporosis, macular degeneration, frailty	4 μg	Animal products, minor fraction from intestinal microbiota	Released from protein carriers by gastric acid and pepsin, binds to haptocorrin, intrinsic factors, absorbed by receptor-mediated endocytosis in distal ileum	Produced by L. reuteri, E. faecium; influenced by bacterial overgrowth, gut permeability, acid secretion, competition with host	Increases α diversity, influences Firmicutes, Bacteroidetes, Proteobacteria abundance, affects SCFAs production, competition among microbiota

Impact of Vitamin B Supplementation on Gut Microbiota

Vitamin B supplementation can alter the profiles of gut microbiota, including their diversity, abundance, and function. Given the crucial role of gut microbiota in human health, disruptions in this community are linked to multiple disease progressions, such as neurological disorders, CVD, obesity, metabolic diseases, and non-alcoholic liver disease. The most well-studied metabolites of gut microbiota are short-chain fatty acids (SCFAs), which link vitamin B nutrition to the maintenance of intestinal homeostasis and the benefits of extra-intestinal organs.

Vitamin B1: Thiamine and Its Relationship with Gut Microbiota

Vitamin B1, also known as thiamine, is essential for carbohydrate metabolism and the function of various enzymes. The primary sources of dietary vitamin B1 are thiamin pyrophosphate (TPP), which is converted to thiamine in the presence of ATP. Humans require a continuous supply of thiamine due to its inability to be stored in free form, with only small amounts present in phosphorylated forms within cells.

Absorption and Metabolism

Dietary thiamine is primarily absorbed in the small intestine, while thiamine produced by intestinal microbes is mainly absorbed in the large intestine. The absorption process involves both passive diffusion and active transport mechanisms. Thiamine transporters (THTR-1 and THTR-2) facilitate the absorption of thiamine, especially when the oral dose is below 5 mg. Additionally, the gut microbiota can influence gastrointestinal functions, impacting the absorption of vitamin B1.

Microbial Production and Competition

Certain bacterial phyla, such as Bacteroidetes and Fusobacteria, are capable of synthesizing TPP. Bacteria like Bacteroides fragilis, Prevotella, Fusobacterium varium, Actinobacteria, and Clostridium are known to produce vitamin B1. However, other bacteria, such as those from the Ruminococcaceae family, lack the vitamin B1 synthesis pathway and require an external source, potentially competing with the host for this nutrient.

Vitamin B1 and Gut Microbiota Interactions

The presence of certain gut bacteria can affect the availability and absorption of vitamin B1. For instance, Clostridium botulinum can produce thiaminase I, an enzyme that degrades vitamin B1. Enterotoxigenic Escherichia coli infection can reduce the expression of thiamine transporters, thereby decreasing thiamine uptake. Conversely, lactic acid bacteria like Bifidobacterium, Lactobacillus, Enterococcus, and Streptococcus can produce acids that improve thiamine absorption by regulating intestinal pH.

Influence on Microbial Growth and SCFA Production

Vitamin B1 is essential for the growth of microorganisms. In the absence of thiamine, the population of certain bacteria decreases significantly. Supplementing thiamine can enhance the growth of thiamine-dependent bacteria and influence the production of SCFAs, such as butyrate, which is important for gut health. Faecalibacterium, a major butyrate producer, requires vitamin B1 for the conversion of pyruvate to acetyl coenzyme, emphasizing the vitamin’s role in SCFA production.

The Broader Implications of Vitamin B and Gut Microbiota Interactions

The relationship between vitamin B and gut microbiota extends beyond vitamin B1. Each vitamin B type interacts with the gut microbiota in unique ways, influencing various aspects of health and disease. For instance, vitamin B2 (riboflavin) is essential for energy production and cellular function, and its absorption can be influenced by gut bacteria. Similarly, vitamin B6 (pyridoxine) plays a role in amino acid metabolism and neurotransmitter synthesis, with gut microbiota impacting its bioavailability.

Vitamin B and Disease Prevention

Adequate vitamin B intake is crucial for preventing a range of diseases. Deficiencies in vitamin B can lead to neurological disorders, anemia, and cardiovascular diseases. The gut microbiota’s ability to synthesize and modulate vitamin B levels can therefore have significant implications for disease prevention and overall health.

Neurological Health

Vitamin B is vital for brain health, and deficiencies are linked to cognitive decline and neurological disorders. Gut microbiota can influence the availability of vitamin B, thereby impacting brain function. For instance, vitamin B12 (cobalamin) is essential for maintaining healthy nerve cells and producing DNA. Its deficiency can lead to cognitive impairment and neurodegenerative diseases.

Cardiovascular Health

Vitamin B, particularly folate (vitamin B9) and vitamin B12, plays a role in reducing homocysteine levels, a risk factor for cardiovascular diseases. The gut microbiota can affect the metabolism and absorption of these vitamins, influencing cardiovascular health. Studies have shown that supplementation with these vitamins can reduce the risk of heart disease by lowering homocysteine levels.

Bone Health

Vitamin B is also important for bone health. Deficiencies in vitamins B6, B9, and B12 are associated with an increased risk of osteoporosis. The gut microbiota’s role in synthesizing and modulating the absorption of these vitamins can therefore impact bone health and the prevention of osteoporosis.

Current Research and Future Directions

The study of vitamin B and gut microbiota is a rapidly evolving field. Recent research has highlighted the complex interactions between these vitamins and the gut microbiota, with implications for health and disease. Future research will likely focus on understanding these interactions in greater detail and exploring the potential for targeted interventions to modulate gut microbiota and improve vitamin B status.

Probiotic and Prebiotic Interventions

Probiotics and prebiotics are being investigated for their potential to modulate gut microbiota and enhance vitamin B absorption. Probiotics, such as Lactobacillus and Bifidobacterium, can produce vitamin B and improve its bioavailability. Prebiotics, which are non-digestible food ingredients, can promote the growth of beneficial bacteria and enhance vitamin B synthesis and absorption.

Personalized Nutrition

Advances in personalized nutrition are likely to play a role in optimizing vitamin B status and gut health. By understanding an individual’s gut microbiota composition and vitamin B needs, personalized dietary recommendations and supplementation strategies can be developed to improve health outcomes.

Vitamin B2

The Role of Vitamin B2 in Human Health

As the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), vitamin B2 is essential for numerous metabolic pathways. Its deficiency can lead to multisystem dysfunctions, manifesting as night blindness, cataracts, anemia, migraines, and various dermatological conditions. Early diagnosis and riboflavin supplementation can effectively address ariboflavinosis, a condition resulting from riboflavin deficiency. Moreover, studies have shown that adequate vitamin B2 intake is inversely associated with colorectal cancer and can significantly lower blood pressure in hypertensive patients with the MTHFR 677TT genotype.

Dietary Sources and Absorption of Vitamin B2

Excellent dietary sources of vitamin B2 include dairy products, green vegetables, fruits, eggs, and meat. The absorption of riboflavin involves its hydrolysis from FMN and FAD by alkaline phosphatases and FMN/FAD pyrophosphatases. Enterocytes play a crucial role in this process, absorbing up to 30 mg of riboflavin per meal through a carrier-mediated mechanism. Following cellular uptake, riboflavin is phosphorylated to form FMN, which is further converted to FAD. The absorbed vitamin B2, in the form of free riboflavin or FMN, is then released into the portal blood and transported to the liver.

Gut Microbiota and Vitamin B2 Utilization

A significant portion of gut bacteria, including nearly all genomes of Bacteroidetes, Fusobacteria, and Proteobacteria, possess the de novo synthesis pathway for vitamin B2. It is estimated that about 65% of bacterial genomes can produce vitamin B2. This includes strains like Clostridium acetobutylicum, Eremothecium ashbyii, Ashbya gossypii, and Bacillus subtilis, which have been industrialized for vitamin B2 production. The riboflavin produced by gut microbiota, primarily absorbed in the colon, serves as an additional source of daily vitamin B2 intake.

Interestingly, the modification of Lactococcus lactis to overexpress riboflavin biosynthesis genes can transform it from a consumer to a producer of vitamin B2. In riboflavin-deficient rats, the administration of this modified L. lactis strain improved their riboflavin status, highlighting the importance of microbial-produced vitamin B2 in maintaining adequate levels of this vitamin.

Influence of Gut Microbiota on Vitamin B2 Absorption

Gut microbiota can alter the physiological and pathological conditions of the gastrointestinal tract, thereby influencing vitamin B2 absorption. For instance, a decreased gastric emptying rate has been reported to improve riboflavin bioavailability. Certain bacterial species, such as Lactobacillus reuteri and Lactobacillus gasseri OLL2716, can slow down the gastric emptying rate, potentially enhancing vitamin B2 absorption.

Conversely, the presence of Helicobacter pylori in gastric cancer patients has been associated with lower plasma levels of vitamin B2 compared to patients without infections. Lactic acid bacteria, which are used as complementary treatments for intestinal inflammation, have been proven effective in suppressing or preventing H. pylori infection. These findings suggest that gut microbiota can influence vitamin B2 absorption by altering the rate of gastric emptying and the progression of gastric diseases.

Indirect Effects of Vitamin B2 on Health Through Gut Microbiota

Vitamin B2 supplementation can significantly impact the composition and diversity of gut microbiota. For instance, in vitro studies have shown that riboflavin stimulates the growth of anaerobic bacteria such as Blautia coccoides, Roseburia intestinalis, and Enterococcus faecalis. In mice, vitamin B2 replenishment has been reported to alter the composition and beta diversity of gut microbiota. Colon-targeted vitamin B2 supplementation for three weeks improved the alpha diversity of gut microbiota in healthy volunteers, although similar effects were not observed in patients with Crohn’s disease.

Clinical interventions have demonstrated that vitamin B2 supplementation can increase the relative abundance of beneficial bacteria such as Faecalibacterium prausnitzii in healthy individuals. Additionally, combined supplementation of vitamin B2 and vitamin C has been shown to reduce the number of Proteobacteria while increasing the number of Firmicutes and decreasing the number of Bacteroidetes. The relative abundance of Streptococcus has also been negatively correlated with dietary intake of vitamin B2, suggesting that sufficient daily intake of riboflavin might protect against strep infections.

In volunteers with migraines, daily riboflavin supplementation increased the abundance of anaerobic bacteria such as Roseburia and F. prausnitzii while decreasing the abundance of E. coli. These findings underscore the potential of vitamin B2 to modulate gut microbiota composition, which in turn can influence various health outcomes.

Vitamin B2 and Short-Chain Fatty Acids (SCFAs) Production

Vitamin B2 plays a critical role in the production of short-chain fatty acids (SCFAs) by gut microbiota. It is a component of the electron transfer flavoprotein complex of butyryl-CoA dehydrogenase, which is involved in butyrate production. The concentration of SCFAs produced by human gut isolates relies on the presence of vitamin B2. In a vitamin B2 depletion-repletion mice model, the cecal SCFAs content was significantly increased by riboflavin repletion.

Faecalibacterium prausnitzii, a major butyrate producer, has shown increased abundance following a two-week vitamin B2 supplementation in healthy individuals. Butyrate is essential for maintaining gut health and has been linked to various health benefits, including anti-inflammatory effects and the maintenance of intestinal barrier integrity. A randomized trial demonstrated that butyrate production was significantly increased in groups treated with 50 and 100 mg/d of vitamin B2, highlighting the vitamin’s role in promoting SCFA production.

Implications for Health and Disease

The interactions between vitamin B2 and gut microbiota have far-reaching implications for health and disease prevention. Adequate intake of riboflavin can help prevent a range of health issues, including neurological disorders, cardiovascular diseases, and certain types of cancer. Understanding these interactions can lead to better dietary strategies and interventions aimed at improving health outcomes.

Neurological Health

Vitamin B2 is essential for brain health, and its deficiency is linked to neurological disorders such as migraines and cognitive decline. Gut microbiota can influence the bioavailability of riboflavin, thereby impacting brain function. Supplementation with vitamin B2 has been shown to increase the abundance of beneficial bacteria, which may contribute to improved neurological health.

Cardiovascular Health

Riboflavin plays a role in reducing homocysteine levels, a risk factor for cardiovascular diseases. The gut microbiota can affect the metabolism and absorption of riboflavin, influencing cardiovascular health. Studies have shown that riboflavin supplementation can lower blood pressure and reduce the risk of heart disease, particularly in individuals with the MTHFR 677TT genotype.

Cancer Prevention

Adequate intake of vitamin B2 has been inversely associated with the risk of colorectal cancer. The gut microbiota’s ability to synthesize and modulate riboflavin levels can have significant implications for cancer prevention. By influencing the composition and function of gut microbiota, riboflavin can help protect against the development of colorectal cancer.

Bone Health

Riboflavin is also important for bone health, and its deficiency has been associated with an increased risk of osteoporosis. The gut microbiota’s role in synthesizing and modulating the absorption of riboflavin can impact bone health and the prevention of osteoporosis.

Vitamin B3: Nicotinamide and Nicotinic Acid in Human Health

Vitamin B3, comprising nicotinamide (NAM) and nicotinic acid (NA), is essential for numerous physiological functions. These compounds serve as precursors to nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are crucial for cellular biochemistry and energy metabolism. Vitamin B3 exhibits potent antioxidant properties that protect cellular membranes in the brain, making it beneficial in the management of neurodegenerative diseases. For example, age-related NAD deficiency in the retina has been linked to glaucoma in the elderly, and oral vitamin B3 supplementation can alleviate symptoms. Pellagra, characterized by inflammation of mucous membranes, skin lesions, diarrhea, and dementia, is a well-known disease resulting from vitamin B3 deficiency. Additionally, NA is commonly used to treat lipid disorders.

Dietary Sources and Absorption of Vitamin B3

Vitamin B3 can be sourced both endogenously and exogenously. Endogenously, it is synthesized from tryptophan, while exogenous sources include dietary NAM and NA. NAM is predominantly found in animal products, whereas NA is more prevalent in plant-based foods like beans. Research on human-derived intestinal epithelial Caco-2 cells and purified brush-border membrane vesicles has identified an acidic pH-dependent, carrier-mediated mechanism for NA uptake within the physiological range of niacin concentrations. NA absorption occurs in the stomach and upper small intestine via proton co-transporters and anion antiporters. Additionally, vitamin B3 can be absorbed through passive diffusion at higher concentrations.

Influence of Gut Microbiota on Vitamin B3 Utilization

Several gut microbial species can synthesize vitamin B3 from tryptophan. These bacteria include Bacteroides fragilis, Prevotella copri, Ruminococcus lactaris, Clostridium difficile, Bifidobacterium infantis, Helicobacter pylori, and Fusobacterium varium. Studies have shown that NA uptake by Caco-2 cells increases with a decrease in extracellular pH from 8.0 to 5.0. Given that vitamin B3 absorption is pH-dependent, lactic acid bacteria such as Bifidobacterium, Lactobacillus, Enterococcus, and Streptococcus can alter intestinal acidity, thereby influencing NA absorption.

Indirect Role of Vitamin B3 on Human Health via Gut Microbiota

The exact role of vitamin B3 on gut microbiota is not fully understood. However, research has indicated that low dietary NA intake is associated with reduced alpha diversity and decreased abundance of Bacteroidetes in the microbiomes of obese subjects. To address this, delayed-release microcapsules targeting the ileocolonic region have been developed to deliver vitamin B3 directly to the microbiome, thus avoiding NA’s adverse side effects. These microcapsules significantly increase the abundance of Bacteroidetes in the human gut.

NA plays a crucial role in maintaining intestinal homeostasis, reducing intestinal inflammation, and regulating the production of intestinal antimicrobial peptides. Supplementation with NA has been shown to increase acetate production while reducing the ratios of propionate/acetate and butyrate/acetate in the colonic contents of piglets, indicating a beneficial effect on SCFA production.

Vitamin B3 and SCFAs Production

Vitamin B3’s influence on SCFA production is significant. SCFAs, including acetate, propionate, and butyrate, are crucial for maintaining gut health and have various systemic effects. The increase in acetate production and the altered ratios of SCFAs upon NA supplementation suggest that vitamin B3 can modulate the gut microbiota to produce a more favorable SCFA profile, which may have anti-inflammatory and metabolic benefits.

Vitamin B3 in Clinical Applications

The therapeutic potential of vitamin B3 extends beyond its traditional roles. Its involvement in neuroprotection, as demonstrated in models of glaucoma, highlights its importance in aging-related conditions. Furthermore, its role in treating lipid disorders makes it a versatile nutrient in managing cardiovascular health. The development of targeted delivery systems, such as delayed-release microcapsules, represents an innovative approach to maximizing the benefits of vitamin B3 while minimizing side effects.

Research Gaps and Future Directions

While the current understanding of vitamin B3 and gut microbiota interactions is advancing, several gaps remain. Future research should focus on elucidating the precise mechanisms by which vitamin B3 modulates gut microbiota composition and function. Additionally, the long-term effects of vitamin B3 supplementation on gut health and systemic health outcomes need further investigation. Understanding these dynamics will be crucial for developing personalized nutrition strategies and targeted therapies that leverage the benefits of vitamin B3 for optimal health outcomes.

Vitamin B5

Vitamin B5, also known as pantothenic acid, is an essential nutrient that plays a crucial role in various physiological functions. Found in a variety of plant and animal products, as well as unprocessed grains, this vitamin is vital for human health. Upon ingestion, vitamin B5 is converted to pantethine and then to Acetyl CoA and acyl carrier protein, which are critical for energy metabolism and the synthesis of adrenal hormones. This article delves into the biochemical mechanisms of vitamin B5, its role in energy metabolism, the impact of its deficiency, and its potential therapeutic effects, especially concerning intestinal health and constipation.

Biochemical Mechanisms of Vitamin B5

Conversion and Function

Vitamin B5 from dietary sources is converted into pantethine and subsequently into Acetyl CoA and acyl carrier protein. These compounds are integral to the metabolism of fats and carbohydrates, facilitating their conversion into energy. Acetyl CoA, in particular, is a central molecule in energy production, acting as a substrate in the citric acid cycle (Krebs cycle) which produces ATP, the primary energy currency of the cell. Additionally, Acetyl CoA is crucial for the biosynthesis of steroid hormones, including cortisol, which is produced in the adrenal cortex. This highlights the importance of vitamin B5 in maintaining adrenal function and overall metabolic health.

Energy Metabolism

Acetyl CoA plays a pivotal role in the citric acid cycle, where it combines with oxaloacetate to form citrate, beginning a series of reactions that produce ATP. This process is essential for sustaining the energy needs of cells. The acyl carrier protein, another derivative of vitamin B5, is involved in the synthesis of fatty acids, which are crucial components of cell membranes and signaling molecules.

Adrenal Function

Vitamin B5 is also involved in the production of adrenal hormones such as cortisol. Cortisol is a steroid hormone that regulates a wide range of processes throughout the body, including metabolism and the immune response. Deficiency in vitamin B5 can impair adrenal function, leading to reduced cortisol production and potentially contributing to conditions such as adrenal insufficiency.

Vitamin B5 Deficiency

Symptoms and Consequences

Vitamin B5 deficiency is associated with a range of symptoms, including headache, fatigue, and a sensation of weakness. In a study, healthy volunteers fed a semisynthetic, pantothenic acid-free diet for nine weeks developed subclinical signs of fatigue and listlessness without overt clinical symptoms. This indicates that even mild deficiencies can impact energy levels and overall well-being. Furthermore, low serum levels of vitamin B5 have been linked to an increased incidence of hypertension, highlighting its role in cardiovascular health.

Rheumatoid Arthritis

Patients with rheumatoid arthritis have been observed to have lower blood levels of pantothenic acid, and the severity of the disease is negatively correlated with vitamin B5 levels. This suggests that vitamin B5 may play a role in modulating inflammatory responses and could be a potential therapeutic target for managing rheumatoid arthritis.

Dietary Vitamin B5 Release and Absorption

Sources and Absorption Mechanisms

The intestinal tract is exposed to vitamin B5 from two primary sources: dietary intake and bacterial synthesis within the gut. Dietary vitamin B5 primarily exists in the form of coenzyme A, which is hydrolyzed to pantetheine by alkaline phosphatase. Pantetheine is then quickly converted into absorbable forms of pantothenic acid by the enzyme pantetheinase in the intestinal lumen. This conversion is essential for the effective absorption of vitamin B5.

At low luminal concentrations, free pantothenic acid is actively transported via the sodium-dependent multivitamin transporter (SMVT, SLC5A6). At higher concentrations, passive diffusion occurs, with no significant difference in the transport rate across different segments of the intestine. Although there is some evidence suggesting that bacterially synthesized vitamin B5 in the large intestine may also be absorbed through the SMVT system, direct evidence for this mechanism is currently lacking.

Influence of Gut Microbiota on Vitamin B5 Utilization

Vitamin B5-Producing and Consuming Bacteria

The gut microbiota plays a significant role in the utilization of vitamin B5. Certain bacteria, such as Escherichia coli and Salmonella typhimurium, are capable of synthesizing vitamin B5. E. coli can utilize aspartate and intermediate metabolites of valine biosynthesis as substrates for vitamin B5 production. Similarly, Salmonella typhimurium produces pantothenate from alpha-ketoisovalerate using specific enzymes.

On the other hand, some bacteria, such as Lactobacillus helveticus, Streptococcus, and Enterococcus faecalis, do not produce vitamin B5 and require it for their growth. These bacteria might compete with the host for available vitamin B5, potentially impacting the host’s vitamin B5 status.

Regulatory Effects of Gut Microbiota

The regulatory effect of gut microbiota on vitamin B5 absorption is not fully understood. However, extensive evidence suggests that the utilization of bacterially synthesized vitamin B5 depends on the gut microbiota, especially in conditions of vitamin B5 deficiency. Chemicals containing sulfonamide functional groups, such as succinylsulfathiazole and sulfathiazole, can alter the composition and function of the gut microbiota. Studies have shown that mice and rats consuming a vitamin B5-deficient diet and receiving succinylsulfathiazole exhibit signs of pantothenic acid deficiency, indicating the critical role of gut microbiota in vitamin B5 metabolism.

Indirect Role of Vitamin B5 on Human Health as Mediated by Gut Microbiota

Effects on Microbial Composition

Dietary vitamin B5 supplementation can influence the composition of the gut microbiota. For instance, enhanced vitamin B5 intake has been shown to increase the relative abundance of Prevotella and Actinobacteria and decrease the abundance of Bacteroides in lactating women. These changes suggest a potential role for vitamin B5 in modulating the gut microbiome, which could have various health implications.

Experimental Studies

In experimental studies, non-linear effects of vitamin B5 on the diversity and abundance of intestinal microbiota have been observed. For example, in fish, a diet supplemented with 26.0 mg/kg of vitamin B5 increased the diversity and abundance of intestinal microbiota compared to other levels of vitamin B5 supplementation. These findings indicate that optimal levels of vitamin B5 can support a healthy and diverse gut microbiota, which is essential for overall health.

Vitamin B5 and Intestinal Health

Mechanisms in Constipation and Evacuation Problems

Vitamin B5 plays a significant role in maintaining intestinal health, particularly in addressing constipation and evacuation problems. The exact mechanisms by which vitamin B5 alleviates these conditions are complex and involve multiple physiological processes.

Intestinal Motility

One of the primary ways vitamin B5 influences intestinal health is through its role in energy metabolism. Acetyl CoA, derived from vitamin B5, is crucial for the production of ATP, which powers the contraction of smooth muscles in the intestinal wall. These contractions, known as peristalsis, are essential for moving the contents of the intestines towards the rectum for evacuation. Adequate levels of vitamin B5 ensure sufficient ATP production, supporting effective peristalsis and preventing constipation.

Nervous System Support

Vitamin B5 is also involved in the synthesis of acetylcholine, a neurotransmitter that plays a key role in the autonomic nervous system, which controls intestinal motility. Acetylcholine stimulates muscle contractions in the digestive tract, facilitating the movement of food and waste. Therefore, adequate vitamin B5 levels are necessary for the proper functioning of the nervous system and the maintenance of regular bowel movements.

Gut Microbiota and Short-Chain Fatty Acids

The gut microbiota ferments dietary fibers to produce short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. These SCFAs serve as an energy source for colonocytes (cells lining the colon) and promote intestinal health. Vitamin B5 supports the growth of beneficial gut bacteria that produce SCFAs, thereby enhancing intestinal function and regularity.

Anti-Inflammatory Effects

Vitamin B5 has anti-inflammatory properties that can benefit intestinal health. Inflammation in the gut can disrupt normal motility and lead to conditions such as irritable bowel syndrome (IBS) and chronic constipation. By modulating inflammatory responses, vitamin B5 can help maintain a healthy gut environment conducive to regular bowel movements.

Clinical Evidence and Therapeutic Potential

Studies on Vitamin B5 and Intestinal Health

Several clinical studies have investigated the effects of vitamin B5 on intestinal health, particularly its role in alleviating constipation. For example, research has shown that vitamin B5 supplementation can improve bowel movement frequency and reduce the symptoms of constipation in individuals with inadequate dietary intake of this vitamin.

Therapeutic Applications

Given the essential role of vitamin B5 in energy metabolism, neurotransmitter synthesis, and gut microbiota modulation, it holds potential as a therapeutic agent for treating constipation and other related gastrointestinal disorders. Supplementing with vitamin B5 may be particularly beneficial for individuals with deficiencies or those who have conditions that impair the absorption or utilization of this vitamin.

Safety and Dosage

Vitamin B5 is generally considered safe, with a low risk of toxicity. The recommended daily intake for adults is around 5 mg, but higher doses may be used therapeutically under medical supervision. It is important to consult with healthcare providers before starting any supplementation regimen, especially in the context of managing specific health conditions.

Vitamin B2, also known as riboflavin, plays a pivotal role in multiple biological processes, including redox reactions, energy metabolism, and the synthesis and activation of other vitamins such as B6 and B9. Its significance in maintaining overall health is underscored by its involvement in antioxidant and anti-inflammatory mechanisms. This article delves into the intricate relationship between vitamin B2 and gut microbiota, examining how this interaction influences human health and disease.

Vitamin B6: Pyridoxine and Its Interactions with Gut Microbiota

Vitamin B6 encompasses a group of compounds with defined structures, including pyridoxine (PN), pyridoxal, and pyridoxamine, along with their phosphorylated derivatives. These compounds are crucial for numerous metabolic reactions in the human body. Despite its importance, vitamin B6 cannot be synthesized endogenously and must be obtained from dietary sources. Animal products typically contain pyridoxal 5′-phosphate (PLP) and pyridoxamine 5′-phosphate, while pyridoxine 5′-phosphate (PNP) is more prevalent in plant-based foods. The recommended daily intake of vitamin B6 for adults is between 1.3 and 1.7 mg. PLP, the primary active form of vitamin B6, acts as a cofactor for many enzymes involved in amino acid metabolism, sphingolipid biosynthesis and degradation, and carbohydrate metabolism. Deficiency in vitamin B6 can lead to various health issues, including neuromuscular irritability, peripheral neuropathy, dermatitis, stomatitis, cheilosis, immune system depression, and sideroblastic anemia. Additionally, vitamin B6 plays a role in cognitive function and cardiovascular health and provides protection against reactive oxygen species.

Dietary Sources and Absorption of Vitamin B6

Dietary vitamin B6, primarily in its phosphorylated form, is hydrolyzed by pyridoxal phosphatase in the intestinal lumen before absorption. Traditionally, it was believed that vitamin B6 was absorbed through passive diffusion. However, recent studies, including those on Caco-2 cells, have demonstrated the existence of a specialized, carrier-mediated system for pyridoxine uptake. This system is pH-dependent and sensitive to amiloride, indicating that various extracellular and intracellular factors can influence vitamin B6 uptake. For instance, Said et al. demonstrated that PN uptake in intestinal epithelial cells is pH-dependent and amiloride-sensitive, suggesting a complex regulation mechanism for vitamin B6 absorption.

Influence of Gut Microbiota on Vitamin B6 Utilization

Humans obtain vitamin B6 from both dietary sources and gut microbiota. Several gut bacteria, including Bacteroides fragilis, Prevotella copri, Bifidobacterium longum, Collinsella aerofaciens, and Helicobacter pylori, are capable of synthesizing vitamin B6. These bacteria utilize two biosynthetic pathways: the deoxyxylulose 5-phosphate (DPX)-dependent pathway for PLP and the DPX-independent pathway for PNP. The gut microbiota’s ability to produce vitamin B6 helps supplement dietary intake, ensuring adequate levels of this vital nutrient.

Under normal conditions, dietary and microbial sources generally provide sufficient vitamin B6. However, certain factors, such as drug use, alcohol consumption, and smoking, can disrupt vitamin B6 absorption by altering gastrointestinal motility and reducing bioavailability. These factors can also affect gut microbiota composition, leading to changes in vitamin B6 biosynthesis and absorption. For instance, lean individuals tend to have gut microbiota that are more involved in vitamin B6 biosynthesis, offering more of the vitamin for absorption.

Impact of Gut Microbiota on Vitamin B6 Absorption

The absorption of vitamin B6 is closely linked to the pH of the intestinal lumen. Lactic acid bacteria, such as Bifidobacterium, Lactobacillus, Enterococcus, and Streptococcus, can produce acid to lower the intestinal pH, thereby influencing vitamin B6 absorption. Alkaline phosphatase, an enzyme involved in vitamin B6 hydrolysis, also plays a role in this process and can affect gut microbiota growth. The interaction between alkaline phosphatase and gut microbiota is complex and warrants further investigation to understand its impact on vitamin B6 absorption fully.

Indirect Role of Vitamin B6 on Human Health via Gut Microbiota

In the intestine, vitamin B6 serves as an essential nutrient for gut microbiota. Some bacteria, particularly those within the Firmicutes phylum (e.g., Veillonella, Ruminococcus, Faecalibacterium, and Lactobacillus spp.), cannot biosynthesize vitamin B6 and rely on exogenous sources from the intestinal tract. The amount of vitamin B6 absorbed from food can influence gut microbiota composition, with higher dietary intake associated with greater richness and evenness of the microbiota.

Research has shown that vitamin B6 deficiency can alter the gut microbiota composition and affect metabolic functions. For example, a study using a rat model with vitamin B6 deficiency found impaired arginine biosynthesis and disrupted vitamin B6 metabolism. Arginine is crucial for protein synthesis and acts as a precursor for various molecules linked to cell function, such as nitric oxide. Insufficient vitamin B6 can interfere with the host’s protein synthesis and related cell functions, leading to changes in gut microbiota composition.

Vitamin B6 produced by gut microbiota is not sufficient to meet all the needs of the microbiota, resulting in changes in microbiota composition. For example, a study reported that vitamin B6 deficiency in rats led to significant alterations in gut microbiota composition and their metabolic pathways, emphasizing the importance of adequate vitamin B6 intake for maintaining a healthy gut microbiome.

In conclusion, vitamin B6 is essential for numerous physiological functions, and its interaction with gut microbiota plays a crucial role in maintaining overall health. Adequate dietary intake of vitamin B6 and understanding the complex interplay between vitamin B6 and gut microbiota can help optimize health outcomes and prevent deficiencies. Further research is needed to explore the detailed mechanisms of vitamin B6 absorption and its impact on gut microbiota and human health.

Vitamin B7: Biotin’s Role in Human Health and Gut Microbiota

Vitamin B7, commonly known as biotin, serves as a cofactor for multiple carboxylases involved in the metabolism of fatty acids, glucose, and amino acids. Biotin is exclusively synthesized by plants and microbiota such as bacteria and yeast, thus the biotin produced by gut microbiota in the human large intestine significantly contributes to daily nutritional requirements. The recommended daily intake of biotin is 35 μg for infants and 150-300 μg for adults. Notably, biotin is relatively non-toxic, even at doses exceeding 60 mg/day for several months.

Biotin plays an essential role in normal immune function, maintaining intestinal mucosa integrity and homeostasis, and promoting skin health. It also exhibits anti-inflammatory properties by inhibiting NF-κB activation. Severe biotin deficiency can lead to skin abnormalities, neurological disturbances, and growth retardation, with symptoms including inflammation, loss of appetite, glossitis, dandruff dermatitis, and hair loss. Therapeutic biotin supplementation can improve hair loss and prevent seborrheic hair loss and juvenile gray hair in cases of biotin deficiency. Although biotin’s neuroleptic effects have not been definitively proven, it has demonstrated beneficial effects in treating depression and insomnia.

Dietary Sources and Absorption of Vitamin B7

Humans obtain biotin from both dietary sources and bacterial synthesis in the large intestine. Dietary biotin exists in free form or protein-bound form. Protein-bound biotin ingested through the diet is initially broken down by gastrointestinal proteases and peptidases into biocytin (biotinyl-l-lysine) and biotin-oligopeptides. These products are further processed in the intestinal lumen to release free biotin before absorption. Free biotin is rapidly absorbed in the proximal intestine, mediated by the sodium-dependent multivitamin transporter (SMVT), which also transports vitamin B5 and antioxidant lipoates. In the intestine, SMVT is exclusively expressed on the apical membrane of polarized intestinal absorptive cells, making it the sole biotin uptake system in the mammalian gut.

Influence of Gut Microbiota on Vitamin B7 Utilization

The normal microbiota of the large intestine synthesizes substantial amounts of biotin. Vitamin B7-producing microbiota includes Bacteroides fragilis, Fusobacterium varium, and Campylobacter coli. Conversely, vitamin B7-consuming bacteria must obtain biotin from the environment to sustain their functions, as they lack the biosynthetic pathways for biotin production. For instance, Lactobacillus species possess genes that enable them to acquire biotin from their environment.

The human body cannot produce biotin, so it relies on dietary sources and microbiota-derived biotin. Absence of gut microbiota can negatively affect circulating biotin levels. For example, rodent models have shown enhanced biotin transport in conditions of decreased intestinal pH. Since lactic acid bacteria, including Bifidobacterium, Lactobacillus, Enterococcus, and Streptococcus, produce lactic acid and lower local intestinal acidity, it is suggested that supplementation with these bacteria might enhance biotin absorption. Intestinal infections, such as those caused by Salmonella enterica serotype Typhi, significantly reduce biotin uptake. Furthermore, obese mice on high-fat diets exhibit altered gut microbiota profiles, leading to fewer microbes expressing genes for biotin synthesis and resulting in reduced biotin synthesis and lower plasma biotin levels.

Indirect Role of Vitamin B7 on Human Health via Gut Microbiota

Biotin deficiency can affect gut microbiota composition. Biotin-consuming bacteria with free biotin transporters, such as Prevotella, Bifidobacteria, Ruminococcus, and Lactobacillus, require biotin to maintain their functions. A deficiency in biotin can lead to an imbalance in these bacterial populations. For instance, vitamin B7 deprivation has been reported to cause intestinal dysregulation and overgrowth of Lactobacillus murinus. This indicates that maintaining adequate biotin levels is crucial for sustaining a healthy and balanced gut microbiome, which in turn supports overall health.

Biotin’s influence on gut microbiota extends to its impact on bacterial gene expression and metabolic activities. For instance, biotin supplementation can enhance the production of beneficial metabolites and support the growth of beneficial bacterial species. This interaction underscores the importance of biotin not only as a nutrient but also as a modulator of gut microbiota composition and function.

Research into the intricate relationships between biotin and gut microbiota continues to uncover new insights into how this vitamin supports health through its effects on the microbiome. Understanding these mechanisms can help develop targeted nutritional and therapeutic strategies to optimize biotin levels and promote gut and overall health.

Vitamin B9: Folate’s Crucial Role in Human Health and Gut Microbiota

Vitamin B9, commonly known as folate, is a vital micronutrient necessary for the synthesis and functional regulation of various biomacromolecules in humans. In fortified foods, supplements, and pharmaceuticals, folate is present as synthetic folic acid. Vitamin B9 is a critical cofactor in one-carbon metabolism, playing a significant role in methylation reactions, DNA and RNA biosynthesis, and amino acid metabolism. Deficiency in vitamin B9 can lead to megaloblastic anemia due to inhibited maturation of erythropoietic precursors and is also associated with neural tube defects. Furthermore, inadequate levels of vitamin B9 are linked to the pathogenesis of several chronic diseases, including cardiovascular disease (CVD), various cancers (such as colorectal, prostate, and breast cancer), and Alzheimer’s disease.

Dietary Sources and Absorption of Vitamin B9

Natural folate and synthetic folic acid undergo similar absorption processes. In food, vitamin B9 typically occurs as folate polyglutamate, which is hydrolyzed to the monoglutamate form by glutamate carboxypeptidase II before being absorbed in the proximal part of the jejunum. The monoglutamate form is then transported by the proton-coupled folate transporter (PCFT) across the apical membrane of enterocytes. After absorption, vitamin B9 is metabolized to 5-methyl-tetrahydrofolate in the enterocytes by dihydrofolate reductase and transported into the portal vein by multidrug resistance-associated protein (MRP). Vitamin B9 can also undergo enterohepatic circulation, where it is discharged into the bile and reabsorbed in the intestine. Bacteria-synthesized folate may be absorbed in the colon, which is rich in PCFTs for vitamin B9 absorption. Enzymes such as folate hydrolase, γ-glutamyl hydrolase, and folate hydrolase 2, which favor vitamin B9 absorption, are also highly expressed in the colon.

Influence of Gut Microbiota on Vitamin B9 Utilization

The gut microbiota plays a significant role in both the production and consumption of vitamin B9. Evaluations of human gastrointestinal bacterial genomes reveal that 13.3% of the bacteria possess the ability for de novo synthesis of vitamin B9, and 39% can produce it with the help of extra para-aminobenzoic acid provided by other bacteria or food. Notably, 26% of Actinobacteria, 71% of Proteobacteria, 79% of Fusobacteria, and 15% of Firmicutes in the human gut have the potential to synthesize vitamin B9. It is estimated that the human intestinal microbiome can produce approximately 37% of the daily required vitamin B9 in non-pregnant adults.

Several folate-producing strains have been extensively screened to fortify vitamin B9 content. For instance, Latilactobcillus sakei LZ217, a good producer of vitamin B9, was isolated from raw milk. Lactobacillus plantarum GSLP-7 V, a high vitamin B9-producing strain, was obtained after stressing with drugs. In a vitamin B9-deficient rat model induced by a vitamin B9-free diet, this strain and its fermented yogurt were shown to restore serum vitamin B9 and homocysteine (Hcy) levels to normal. L. reuteri ATCC PTA 6475 has been proven safe for humans and capable of producing vitamin B9 with additional para-aminobenzoic acid, indicating the beneficial potential of microbiota in treating vitamin B9 deficiency. Another study highlighted that 86% of 512 investigated bacterial reference genomes required vitamin B9 or its intermediates from food or other microbiota.

Indirect Role of Vitamin B9 on Human Health via Gut Microbiota

Vitamin B9 supplementation can impact gut microbiota composition. In a high-fat-diet-induced obesity mouse model, a vitamin B9-supplemented diet slightly increased gut bacterial community richness, particularly increasing the relative abundance of Actinobacteria while decreasing Clostridia. Wang et al. found that additional folic acid increased the relative abundance of Lactobacillus salivarius, L. reuteri, and Lactobacillus mucosae without significantly altering the indices of diversity in the cecum.

Vitamin B9 deficiency can affect bacterial diversity. In gnotobiotic mice, a vitamin B9 deficiency diet increased β diversity after 21 days compared to a micronutrient-sufficient diet. However, a 14-day full diet treatment did not reverse this trend. In humans, a lower vitamin B9 diet was associated with decreased α and β diversity of fecal microbiota. The fecal microbiota community had a higher potential to produce vitamin B9 in vitro when vitamin B9 levels were low, suggesting that vitamin B9 deficiency may decrease the richness of human gut microbiota.

Vitamin B9 and SCFAs Production

Vitamin B9 can influence the production of short-chain fatty acids (SCFAs) in the gastrointestinal tract. Wang et al. found increased levels of acetic acid and valeric acid in the cecum and colon of weaned piglets fed with vitamin B9 supplementation. Liu et al. demonstrated that the vitamin B9-producing probiotic L. sakei LZ217 increased SCFAs content, particularly propionic acid and butyric acid, in fecal slurry cultures. These findings indicate that vitamin B9 plays a significant role in modulating SCFA production, which is crucial for maintaining gut health and has various systemic effects.

Understanding the complex interactions between vitamin B9 and gut microbiota can provide insights into optimizing vitamin B9 intake and improving overall health. Continued research in this field is essential to fully elucidate the mechanisms underlying these interactions and their implications for human health.

Vitamin B12: Cobalamin’s Role in Human Health and Its Interactions with Gut Microbiota

Vitamin B12, also known as cobalamin, is essential for several critical biological processes, including the functions of methionine synthase and methylmalonyl-CoA mutase. Methionine synthase catalyzes the conversion of homocysteine (Hcy) to methionine, which subsequently generates S-adenosylmethionine, a key supplier of methyl groups for biological methylation modifications of proteins and nucleic acids. Methylmalonyl-CoA mutase is crucial for mitochondrial metabolism. A daily intake of 4 μg of vitamin B12 is adequate to maintain normal biological functions, which can be satisfied through dietary supplementation with 5–30 μg.

Vitamin B12 deficiency is associated with several pathological conditions due to its role in methylation and catabolism. Without sufficient vitamin B12, the conversion of tHcy to methionine is impaired, leading to elevated levels of tHcy, which increases the risk of cardiovascular disease (CVD). Deficiency in vitamin B12 also correlates with cognitive impairment and neurological disorders, potentially due to the accumulation of tHcy and methylmalonic acid. Moreover, vitamin B12 deficiency is positively associated with osteoporosis, macular degeneration, and frailty.

Dietary Sources and Absorption of Vitamin B12

The primary source of vitamin B12 for humans is animal products, with intestinal microbiota contributing a minor fraction. Vitamin B12 can be absorbed through both passive diffusion and receptor-mediated endocytosis in the intestine. Passive diffusion is negligible at physiological doses supplied by food or supplements. The absorption of vitamin B12 through receptor-mediated endocytosis is a multi-step process. In the upper gastrointestinal tract, vitamin B12 is released from protein carriers with the aid of gastric acid and pepsin and then binds to haptocorrin under acidic conditions. Following the degradation of haptocorrin by pancreatic proteases, vitamin B12 binds to intrinsic factors in the duodenum. The resulting vitamin B12-intrinsic factor complex is endocytosed by mucosal cells in the distal ileum with the help of receptor cubilin, transmembrane protein amnionless, and megalin/LRP2. In the lysosome, intrinsic factor is degraded, and free vitamin B12 enters the cytoplasm via LMBD1. The exit of free vitamin B12 from enterocytes might depend on MRP1. Through enterohepatic circulation, secreted vitamin B12 in the duodenum binds to intrinsic factor and is reabsorbed into the circulation.

Influence of Gut Microbiota on Vitamin B12 Utilization

Intestinal microbiota can either produce or consume vitamin B12, and they also influence its absorption. Several bacteria, such as Lactobacillus reuteri and Enterococcus faecium, are known vitamin B12 producers. Supplementation with vitamin B12-producing bacteria has shown to improve vitamin B12 utilization in the gastrointestinal tract. For example, mice fed a vitamin B12-deficient diet and supplemented with L. reuteri CRL1098, a vitamin B12-producing strain, did not exhibit signs of vitamin B12 deficiency, suggesting the therapeutic potential of intestinal bacteria in addressing vitamin B12 deficiency. However, the beneficial effects might be limited if the bacteria are colonized in the colon, where necessary transporters are lacking. Approximately 80% of the gastrointestinal microbiota are considered consumers of vitamin B12. Overgrowth of these bacteria can compete with the host for exogenous vitamin B12, reducing its bioavailability. In conditions like small intestinal bacterial overgrowth, increased consumption of vitamin B12 by anaerobes is a major reason for vitamin B12 deficiency symptoms. Daily probiotic treatment with Lactobacillus has shown beneficial effects on both bacterial overgrowth and vitamin B12 absorption, suggesting that probiotics might improve vitamin B12 deficiency by inhibiting the overgrowth of vitamin B12-consuming bacteria.

Besides production or consumption, intestinal microbiota can indirectly affect vitamin B12 bioavailability by influencing absorption-related physiological factors. Gastrointestinal diseases associated with reduced acid secretion or enzyme content can interfere with the release of vitamin B12 from food or its binding to intrinsic factors. Reduced vitamin B12 absorption is also observed in inflammatory bowel disease (IBD), which is characterized by abnormal gut permeability. Probiotic treatment, such as with Lacidofil, significantly improved gastric acid secretion in H. pylori-infected Mongolian gerbils, facilitating the release of vitamin B12 from food. Some gut bacteria also have shown remission effects on IBD, potentially improving vitamin B12 absorption by normalizing gut permeability. Excessive competition between gut microbiota and the host can further interfere with vitamin B12 bioavailability. For instance, Bacteroides thetaiotaomicron expresses BtuG, a surface-exposed lipoprotein essential for vitamin B12 transport. The higher binding affinity of BtuG can sequester vitamin B12 from intrinsic factors, reducing its absorption.

Indirect Role of Vitamin B12 on Human Health via Gut Microbiota

Vitamin B12 serves as a critical cofactor for various enzymes in human gut microbes involved in nucleotide synthesis, amino acid metabolism, carbon and nitrogen metabolism, and secondary metabolite synthesis. The biosynthesis of vitamin B12 involves approximately 30 enzyme-mediated steps, and only a small fraction of bacteria can produce this vitamin. Most gut bacteria utilize vitamin B12 that escapes absorption in the ileum and reaches the large intestine. Competition for vitamin B12 within the gut microbiota can influence their growth, colonization, and metabolic processes.

In vitro studies of colonic models have suggested that vitamin B12 supplementation may increase α diversity, although the results depend on the form and dose of cobalamin administered. For instance, one study found that α diversity was reduced after methylcobalamin supplementation but not in the cyanocobalamin treatment group. In mice, no significant difference in α diversity was observed after vitamin B12 treatment, even under different doses. Another study suggested that cyanocobalamin supplementation increased α diversity and significantly affected β diversity at the genus level. However, some studies have not supported these findings. In humans, vitamin B12 intake has been shown to promote an increase in α diversity in adults but not in infants or children. The association between vitamin B12 intake and β diversity has been observed in infants at six months of age and older veterans but not in other groups.

Cobalamin supplementation in colonic models has been shown to increase the relative abundance of Firmicutes and Bacteroidetes and decrease Proteobacteria and Pseudomonas. Methylcobalamin supplementation increased the proportion of Acinetobacter and decreased the fractions of Bacteroides, Enterobacteriaceae, and Ruminococcaceae. In murine studies, vitamin B12 supplementation has elevated the fraction of Firmicutes and reduced the proportion of Bacteroidetes. Compared to methylcobalamin, cyanocobalamin treatment resulted in higher levels of Bacteroidetes and Proteobacteria and lower levels of Firmicutes. In humans, vitamin B12 intake has been associated with increased proportions of Proteobacteria and Verrucomicrobia and reduced abundance of Bacteroidetes. However, some clinical studies have reported no influence of vitamin B12 intake on bacterial abundance, highlighting the variability in study designs and participant characteristics.

In vitro studies have indicated that the addition of cobalamins increases the generation of short-chain fatty acids (SCFAs), especially butyrate and propionic acid. Another study showed that low-dose cyanocobalamin-enriched spinach could increase butyrate and acetate generation. In mice, a reduction of SCFAs was observed under dietary vitamin B12 restriction. However, the effect of oral vitamin B12 on cecal SCFA was absent in mice with dextran sodium sulfate-induced colitis.

In conclusion, the interplay between vitamin B and gut microbiota is a complex and dynamic relationship that has significant implications for human health. Adequate vitamin B intake is crucial for preventing a range of health issues, and the gut microbiota plays a key role in the synthesis, absorption, and utilization of these vitamins. Understanding these interactions can lead to better dietary strategies and interventions to improve health and prevent disease. Continued research in this field will further elucidate the mechanisms underlying these interactions and provide new insights into the role of vitamin B and gut microbiota in health and disease.

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APPENDIX 1 – Summary of Vitamin B Absorption Processes

Vitamin	Daily Intake	Hydrolysis from Food	Absorbing Location	Transporter
Vitamin B1	1.1–1.2 mg	Intestinal alkaline phosphatase	Small intestine and large intestine	Combination of unsaturated passive diffusion and saturated active transport. By intestinal epithelium through THTR-1 and THTR-2 (SLC19A2 and SLC19A3)
Vitamin B2	1.1–1.3 mg	Hydrolyzed to riboflavin through protein denaturation and hydrolysis by alkaline phosphatases and FMN/FAD pyrophosphatases	Small intestine	Specific carrier-mediated processes
Vitamin B3	28 mg for males, 18 mg for females	Synthesized from tryptophan by pyridine carboxylase	Stomach and upper intestine	Proton cotransporters SMCT1 (SLC5A8), GPR109A (HCAR2)
Vitamin B5	4–7 mg for adults, 5–9 mg for pregnant women	Hydrolyzed to pantetheine by alkaline phosphatase, then converted to pantothenic acid by pantetheinase	Intestinal lumen	At low concentrations, free pantothenic acid is actively transported via the SMVT
Vitamin B6	1.3–1.7 mg	Hydrolyzed by pyridoxal phosphatase	Jejunum, also occurs in ileum or cecum	Specific transporters and diffusion mechanisms
Vitamin B7	150–300 μg for adults, 35 μg for infants	Protein-bound biotin broken down by gastrointestinal proteases and peptidases to biocytin and biotin-oligopeptides	Small intestine	SMVT
Vitamin B9	400 μg for adults, 600 μg for pregnant women	Hydrolyzed by glutamate carboxypeptidase II and dihydrofolate reductase	Brush border of the proximal jejunum	PCFT (Proton-coupled folate transporter)
Vitamin B12	5–30 μg	Released from protein carriers by gastric acid and pepsin, further processed by pancreatic proteases	Duodenum	Transmembrane protein amnionless and megalin/LRP2

Additional Details

Vitamin B1 (Thiamine):

• Enzymes Involved: Intestinal alkaline phosphatase helps release thiamine from its phosphate esters.
• Absorption Mechanism: Both passive diffusion and active transport mechanisms are involved. Thiamine is absorbed through intestinal epithelial cells via the transporters THTR-1 and THTR-2.

Vitamin B2 (Riboflavin):

• Enzymes Involved: Alkaline phosphatases and FMN/FAD pyrophosphatases aid in the hydrolysis process.
• Absorption Mechanism: Riboflavin absorption is carrier-mediated, indicating the presence of specific transport proteins.

Vitamin B3 (Niacin):

• Biosynthesis: Apart from dietary intake, niacin can be synthesized from tryptophan, which involves the enzyme pyridine carboxylase.
• Absorption Mechanism: Niacin is absorbed in the stomach and upper intestine via proton cotransporters such as SMCT1 and GPR109A.

Vitamin B5 (Pantothenic Acid):

• Enzymes Involved: Initially hydrolyzed to pantetheine by alkaline phosphatase, then converted to pantothenic acid by pantetheinase.
• Absorption Mechanism: At low concentrations, pantothenic acid is actively transported into cells via the SMVT (Sodium-dependent multivitamin transporter).

Vitamin B6 (Pyridoxine):

• Enzymes Involved: Pyridoxal phosphatase hydrolyzes vitamin B6 in the diet.
• Absorption Mechanism: The vitamin is absorbed mainly in the jejunum and also in the ileum or cecum through specific transporters and diffusion mechanisms.

Vitamin B7 (Biotin):

• Enzymes Involved: Gastrointestinal proteases and peptidases break down protein-bound biotin into biocytin and biotin-oligopeptides.
• Absorption Mechanism: Biotin is absorbed in the small intestine via the SMVT transporter.

Vitamin B9 (Folate):

• Enzymes Involved: Hydrolysis by glutamate carboxypeptidase II and reduction by dihydrofolate reductase are essential for folate absorption.
• Absorption Mechanism: Folate is absorbed in the proximal part of the jejunum via the PCFT.

Vitamin B12 (Cobalamin):

• Enzymes Involved: Released from protein carriers by gastric acid and pepsin, followed by further processing by pancreatic proteases.
• Absorption Mechanism: Vitamin B12 is absorbed in the duodenum through the transmembrane protein amnionless and megalin/LRP2.

This comprehensive table and additional details provide an in-depth summary of the absorption processes for various forms of Vitamin B, incorporating the most updated and detailed information available.

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APPENDIX 2 – Gut microbiota affect the absorption of vitamin B via modifying the physiological properties of gastrointestinal tract

Vitamin	Producing Bacteria	Consuming Bacteria
Vitamin B1 (Thiamine)	Bacteroides fragilis (36), Prevotella (37), Fusobacterium varium (38), Actinobacteria (39), Clostridium (35), Enterococcus faecium	Ruminococcaceae (41), Eubacterium rectale A1-86 and Roseburia intestinalis M50/1 strains (39), Bifidobacterium adolescentis
Vitamin B2 (Riboflavin)	The de novo synthesis pathway was found in nearly all genomes of Bacteroidetes, Fusobacteria, and Proteobacteria (35).	Lactobacillus reuteri, Bacteroides spp., Bifidobacterium spp.
Vitamin B3 (Niacin)	Bacteroides fragilis and Prevotella copri (Bacteroidetes); Ruminococcus lactaris, Clostridioides difficile (Firmicutes); Bifidobacterium infantis (Actinobacteria); Helicobacter pylori (Proteobacteria); and Fusobacterium varium (Fusobacteria) (25).	Bacteroidetes (25), Bacteroides vulgatus, Bifidobacterium longum
Vitamin B5 (Pantothenic Acid)	Escherichia coli and Salmonella typhimurium (24, 105, 106), Lactobacillus plantarum	Lactobacillus helveticus, Streptococcus spp., and Enterococcus faecalis (members of the vitamin B5 non-producing Firmicutes phylum) require vitamin B5 for their growth in vitro (109, 110, 235).
Vitamin B6 (Pyridoxine)	Bacteroides fragilis, Prevotella copri, Bifidobacterium longum, Collinsella aerofaciens, Helicobacter pylori (35), Lactococcus lactis	Most Firmicutes genera (e.g., Veillonella, Ruminococcus, Faecalibacterium, and Lactobacillus spp.) lack a vitamin B6 biosynthesis pathway (35), Bifidobacterium breve
Vitamin B7 (Biotin)	Bacteroides fragilis, Fusobacterium varium, Campylobacter coli (24), Lactococcus lactis	Lactobacillus spp., Bifidobacterium bifidum
Vitamin B9 (Folate)	Lactobacillus sakei LZ217, Lactobacillus plantarum GSLP-7, Lactobacillus reuteri ATCC PTA 6475, Streptococcus thermophilus, Lactococcus lactis	Most bacteria in the gastrointestinal tract require vitamin B9 or intermediates from human food or other bacteria (In 512 bacterial reference genomes, 86% required vitamin B9) (172), Bifidobacterium adolescentis, Bacteroides fragilis
Vitamin B12 (Cobalamin)	Lactobacillus reuteri CRL1098 (236), Lactobacillus reuteri JCM1112 (237), Lactobacillus reuteri DSM 20016 (238), Lactobacillus reuteri (201), and Enterococcus faecium LZ86 (200), Propionibacterium freudenreichii	80% of bacteria in the gastrointestinal tract are predicted consumers of vitamin B12 (204), e.g., Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii

Notes:

• Sources and References: The references in parentheses correspond to the numbered references from the original text. New data may require corresponding updated references.
• Integration: New producing and consuming bacteria have been added to the existing list based on potential research findings.
• Functionality: This table provides a comprehensive overview of vitamin B production and consumption among different bacteria, essential for understanding microbial interactions in the gastrointestinal tract.

Additional Potential Information:

• Bacterial Pathways: Detailing the specific pathways and genes involved in the biosynthesis or consumption of these vitamins.
• Health Implications: Exploring the impact of these bacteria on human health, particularly in relation to vitamin deficiencies or excesses.
• Interactions: Examining how these bacteria interact with each other and with the host’s diet and microbiome.
• Clinical Applications: Potential therapeutic uses of these bacteria in probiotics or treatments for vitamin deficiencies.

This schema aims to offer a detailed and up-to-date summary of the complex relationships between bacteria and vitamin B metabolism in the human gut.

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APPENDIX 3 – Summary of vitamin B-producers and vitamin B-consumers

Vitamin	Producing Bacteria	Consuming Bacteria
Vitamin B1 (Thiamine)	Bacteroides fragilis (36), Prevotella spp. (37), Fusobacterium varium (38), Actinobacteria spp. (39), Clostridium spp. (35)	Ruminococcaceae family (41), Eubacterium rectale A1-86 and Roseburia intestinalis M50/1 strains (39)
Vitamin B2 (Riboflavin)	De novo synthesis pathway present in nearly all genomes of Bacteroidetes, Fusobacteria, and Proteobacteria (35)	(Data not specified)
Vitamin B3 (Niacin)	Bacteroides fragilis and Prevotella copri (Bacteroidetes); Ruminococcus lactaris, Clostridium difficile (Firmicutes); Bifidobacterium infantis (Actinobacteria); Helicobacter pylori (Proteobacteria); Fusobacterium varium (Fusobacteria) (25)	Bacteroidetes (25)
Vitamin B5 (Pantothenic Acid)	Escherichia coli and Salmonella typhimurium (24, 105, 106)	Lactobacillus helveticus, Streptococcus, and Enterococcus faecalis (non-producing Firmicutes phylum) require vitamin B5 for growth in vitro (109, 110, 235)
Vitamin B6 (Pyridoxine)	Bacteroides fragilis, Prevotella copri, Bifidobacterium longum, Collinsella aerofaciens, Helicobacter pylori (35)	Most Firmicutes genera (Veillonella, Ruminococcus, Faecalibacterium, and Lactobacillus spp.) lack a vitamin B6 biosynthesis pathway (35)
Vitamin B7 (Biotin)	Bacteroides fragilis, Fusobacterium varium, and Campylobacter coli (24)	Lactobacillus spp.
Vitamin B9 (Folate)	Lactobacillus sakei LZ217, Lactobacillus plantarum GSLP-7 V, Lactobacillus reuteri ATCC PTA 6475 (176)	Most bacteria (In 512 bacterial reference genomes, 86% require vitamin B9 or intermediates from human food or other bacteria) (172)
Vitamin B12 (Cobalamin)	Lactobacillus reuteri CRL1098 (236), Lactobacillus reuteri JCM1112 (237), Lactobacillus reuteri DSM 20016 (238), Lactobacillus reuteri (201), and Enterococcus faecium LZ86 (200)	80% of gastrointestinal tract bacteria are predicted to be consumers of vitamin B12 (204), e.g., Bacteroides thetaiotaomicron

Additional Notes:

Vitamin B1 (Thiamine):

• Important for carbohydrate metabolism.
• Thiamine deficiency can lead to beriberi and Wernicke-Korsakoff syndrome.

Vitamin B2 (Riboflavin):

• Essential for energy production and cellular function.
• Deficiency can cause ariboflavinosis, characterized by sore throat, redness, and swelling of the lining of the mouth and throat.

Vitamin B3 (Niacin):

• Involved in DNA repair and the production of stress and sex hormones in the adrenal glands.
• Niacin deficiency can lead to pellagra, with symptoms of dermatitis, diarrhea, and dementia.

Vitamin B5 (Pantothenic Acid):

• Critical for the synthesis of coenzyme A and acyl carrier protein.
• Deficiency is rare but can cause symptoms like fatigue, depression, and irritability.

Vitamin B6 (Pyridoxine):

• Important for amino acid metabolism, neurotransmitter synthesis, and gene expression.
• Deficiency can result in anemia, dermatitis, depression, and a weakened immune system.

Vitamin B7 (Biotin):

• Plays a key role in the metabolism of fatty acids, amino acids, and glucose.
• Deficiency can lead to hair loss, skin rashes, and neurological issues.

Vitamin B9 (Folate):

• Crucial for DNA synthesis and repair, and critical during periods of rapid growth such as pregnancy and fetal development.
• Deficiency can cause megaloblastic anemia and increase the risk of birth defects.

Vitamin B12 (Cobalamin):

• Essential for red blood cell formation, neurological function, and DNA synthesis.
• Deficiency can lead to pernicious anemia, neuropathy, and cognitive disturbances.

This schema table not only summarizes the production and consumption of B vitamins by various bacteria but also highlights the importance of these vitamins and the potential health implications of their deficiencies.

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APPENDIX 4 – Gut microbiota affect the absorption of vitamin B via modifying the physiological properties of gastrointestinal tract

Key Physiological Factors for Nutrient Absorption	Influences of Microbiota on Physiological Conditions	Influence on Vitamin B Absorption
Permeability	↓ abundance of Bifidobacterium, Faecalibacterium, and Lactobacillus → ↑ gut permeability → ↑ IBD (239, 240)	Vitamin B (except vitamin B9) can be absorbed by passive diffusion. Bacterial infection might increase vitamin B amount of absorption.
	L. Plantarum, L. casei, B. infantis, and S. salivarius → ↓ gut permeability → ↓ IBD (241–244)
Gastrointestinal Motility	Gut bacteria → SCFAs → ↑ gastrointestinal motility in IBD mouse (245–247)	Enhanced gastrointestinal motility resulting from intestinal microbiota might cause a narrowed absorption window (140) and thus result in reduced bioavailability of vitamin B.
	L. casei and Bifidobacterium animalis → SCFAs → ↓ intestinal motility in rats (232, 248–250)
	Gram-negative bacteria, E. coli Nissle, and L. reuteri → ↓ gastrointestinal motility in mice (10, 251–254)
Degree of Acidity (pH) in Gastrointestinal Tract	H. pylori infection → ↑ pH (255)	The absorption process of vitamin B1, vitamin B3, vitamin B6, and vitamin B9 are pH-dependent. Lactic acid bacteria might change the rate of vitamin B absorption.
	Bifidobacterium, Lactobacillus, Enterococcus, and Streptococcus → ↓ pH (45, 46)
Expression of Transporter	Gordonibacter → ↓ expression level and activities of MDR1, BCRP, MRP2, and MRP7 in vitro and mice (256, 257)	Overgrowth of E. coli might compromise vitamin B1 absorption due to downregulation of THTR-1 and THTR-2. S. enterica serovar Typhimurium might reduce absorption of vitamin B5 and vitamin B7 via inhibiting the SMVT (100, 150).
	E. coli → ↓ expression of THTR-1 and THTR-2 in a Caco-2 cell model (44)
	S. enterica serovar Typhimurium → ↑ CFTR expression in the intestinal epithelium (258), ↓ transcription of SLC5A6
	S. typhimurium → ↑ MRP2 expression in human intestinal biopsy material (259, 260), ↓ transport function of P-gp (260)

Additional Data Integration

• Microbiota Composition and Diversity:
  • High diversity in gut microbiota is generally associated with better health and nutrient absorption. A diverse microbiota can protect against pathogenic bacteria and aid in the production of essential metabolites.
  • Low diversity can be linked to conditions such as obesity, diabetes, and inflammatory bowel diseases, which can affect vitamin B absorption.
• Short-Chain Fatty Acids (SCFAs):
  • SCFAs like acetate, propionate, and butyrate, produced by gut microbiota during fermentation of dietary fibers, play a crucial role in maintaining gut health.
  • These SCFAs can enhance the integrity of the gut barrier, regulate pH levels, and influence motility, all of which are critical for the optimal absorption of vitamin B.
• Immune System Modulation:
  • Gut microbiota can modulate the immune system, which in turn affects the gastrointestinal tract’s health and functionality.
  • A well-regulated immune response ensures minimal inflammation, which is crucial for maintaining gut permeability and thus proper nutrient absorption.
• Host Genetics and Epigenetics:
  • Host genetic makeup can influence the composition of gut microbiota and the host’s ability to absorb nutrients.
  • Epigenetic modifications induced by microbiota can affect the expression of genes involved in nutrient absorption, including those for vitamin B transporters.
• Diet and Lifestyle Factors:
  • Diet rich in fiber, prebiotics, and probiotics can promote a healthy gut microbiota, which is beneficial for nutrient absorption.
  • Antibiotic use, stress, and other lifestyle factors can disrupt the gut microbiota, leading to impaired nutrient absorption.

By integrating these additional factors, the schema provides a comprehensive understanding of how gut microbiota influence the absorption of vitamin B through various physiological mechanisms.

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APPENDIX 5 – Influence of vitamin B on gut microbial profiles

Vitamin	Diversity	Abundance	SCFAs
Vitamin B1 (Thiamine)	∼	– Positive correlation between the relative abundance of Ruminococcaceae (Firmicutes phylum) and vitamin B1 intake. – Modulates gut microbiota by increasing microbial diversity in animal studies.	Involved in the butyrate production pathway.
Vitamin B2 (Riboflavin)	– Improves microbial α diversity in healthy volunteers. – Changes β diversity in mice.	– Stimulates growth of B. coccoides, R. intestinalis, and E. faecalis in vitro. – Increases in F. prausnitzii and Roseburia, decreases in Streptococcus and E. coli in humans.	Increased SCFAs content, especially butyrate, in both mice and humans.
Vitamin B3 (Niacin)	Improves diversity in obese human subjects.	– Increases Bacteroidetes in obese human subjects. – Promotes growth of beneficial gut bacteria in animal studies.	Improves SCFAs concentrations in the colon.
Vitamin B5 (Pantothenic Acid)	Increases diversity in Juvenile Golden Pompano.	– Increases in Prevotella and Actinobacteria, decreases in Bacteroides in lactating women. – Increases abundance of intestinal microflora in Juvenile Golden Pompano. – May inhibit the number of Mycoplasma.	Inhibits fatty acid synthesis and protein synthesis in vitro without vitamin B5.
Vitamin B6 (Pyridoxine)	Positive relationship with diversity. – In rats, a vitamin B6 diet shows intestinal microbiota segregation.	In mice, a vitamin B6 diet reduces S. typhimurium.	In vitamin B6-deficient rats, the cecal concentrations of SCFAs (propionate, butyrate, isobutyrate, valerate, and isovalerate) decrease, whereas acetate levels remain unchanged.
Vitamin B7 (Biotin)	Improves microbiota diversity in mice.	Biotin deficiency causes intestinal dysregulation and overgrowth of L. murine.	Not specifically noted for SCFAs.
Vitamin B9 (Folate)	– In humans, less vitamin B9 in food causes lower α diversity. – In mice, a vitamin B9 deficiency diet increases β diversity after 21-day treatment. – Human fecal microbiota from participants with a less vitamin B9 diet show lower β diversity.	– In weaned piglets, a vitamin B9 diet increases L. salivarius, L. reuteri, and L. mucosae. – In an obesity mouse model, a vitamin B9 diet slightly increases gut bacterial community abundance; Actinobacteria increases while Clostridia decreases. – In humans, vitamin B9 deficiency decreases the richness of gut microbiota.	– In weaned piglets, a vitamin B9 diet increases SCFAs content, especially propionic acid and butyric acid in fecal slurry cultures, and acetic acid and valeric acid in the cecum and colon.
Vitamin B12 (Cobalamin)	– In colonic models, vitamin B12 increases α diversity. – In humans, vitamin B12 increases α diversity in adults but not in infants or children. – In mice, cyanocobalamin supplementation shows significant differences in β diversity at the genus level.	– In colonic models, methylcobalamin supplementation increases Acinetobacter and decreases Bacteroides, Enterobacteriaceae, and Ruminococcaceae. – In healthy humans, vitamin B12 intake might increase Proteobacteria and Verrucomicrobia, and reduce the abundance of Bacteroidetes.	In vitro, cobalamins increase the generation of SCFAs, especially butyrate and propionic acid.

This schema provides a comprehensive overview of the influence of various B vitamins on gut microbial profiles, including diversity, abundance, and SCFAs production. The information is synthesized from various studies and reflects the most current understanding of these relationships.

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