Understanding the complexity of the human microbiome may help unlock mysteries behind health and psychological illnesses

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Bacteria are at the center of all life forms on planet earth and are the essential building blocks that make living organisms the way they are.

Both the mitochondrion — found in most organisms, which generates energy in the cell — and the chloroplast — the solar energy-harvester located in plants — can be traced to their bacterial ancestors.

These specialized microbes laid the foundation for the biodiversity we live amongst.

Microbes are a part of all multicellular organisms, where they perform a myriad of functions essential to life, including the digestion of nutrients and signaling processes.

The microbes that are an integral component of living organisms are referred to as the microbiome.

The microbiome is found in creatures as simple as the hydra and as complex as humans, elephants, and trees.

Human microbiome

Microbes are part of humans from the initial stage of development and play an important role in the functioning of the human body.

The human microbiome is composed of viruses, bacteria, and fungi residing in communities within and on the body.

Even though these microbes have always been part of the human anatomy, they were visualized only recently with technological advances like molecular imaging tools and next-generation genetic sequencing.

We can now visualize these microbial entities as they operate and execute vital tasks.

The human microbiome is one of the largest organs, weighing approximately two to three kilograms in an adult.

Although it is invisible, the microbiome makes its physical presence evident with occasional noises and smells.

The microbiome bestows on us the unique traits we possess.

The make-up of the microbiome changes during our life span, and a decrease in the number and diversity of its constituents is associated with diseases and ageing. In fact, healthy individuals and centenarians are known to house a wider diversity of microbial partners than unhealthy individuals.

Location-specific functions

The microbiome works in harmony with various organs in the body and aids in the proper functioning of a human being.

For example, microbes living on the surface of the skin guard against invasion from opportunistic bacteria and pathogens.

 These microbes also help in healing wounds, fortifying the immune system and producing volatile signaling molecules essential for communication within the body and the nervous system.

The gut, which harbors the highest amount of microbes, would not be able to carry out its digestive duty without microbial assistance.

Microbes in the gut possess a variety of enzymes dedicated to the digestion of complex carbohydrates and the extraction of nutrients from the foods we consume.

An average person consumes up to 60 tonnes of food during his or her lifespan.

A digestive tract devoid of microbes would require even more food, a situation the world would prefer to do without.

Intestinal microbes also produce vitamins like B12 (pivotal for metabolic activity), hormones, neurotransmitters and a plethora of metabolites integral to normal bodily processes.

They also play an active role in the fate of medications we ingest. In fact, drugs taken orally interact with the gut microbiome first before reaching their intended targets.

This shows a drawing of the human body

The microbiome is the largest organ you may have never heard of, weighing up to three kilograms.

The image is credited to Vasu Appanna.

The molecular entities, like short-chain fatty acids, derived from the microbiome are part of our normal development process.

Microbes are unique to both the individual and the site on the body where they are lodged. For instance, the oily forehead tends to be the preferred residence of Propionibacteria while the moist nose is populated by Corynebacteria.

The stomach possesses acid-tolerant bacteria while the colon harbours anaerobic dwellers.

Understanding the microbiome

This invisible organ is modulated by disparate factors including parental genetics, geography, food and lifestyle.

Although microbiome finger-printing is in its infancy, it is clear that an individual living in an urban area will house a different microbial community relative to a rural inhabitant.

As the microbiome is like any other organ, the disruption of its cellular components — known as dysbiosis— can trigger a range of ailments like obesity, irritable bowel syndrome, dermatitis and neurological imbalance. Some of these diseases can be cured by the use of probiotics and prebiotics designed to adjust microbial imbalance.

Although this expansive invisible organ was visualized only recently, the unravelling of its functions, coupled with the understanding of its origins, could lead to major changes in health care, health education, nutrition and personal traits.

The identification of each microbial constituent and its role will enable the classification of each individual according to his or her microbe type; this has the potential to be as revolutionary as the discovery of blood groups in the twentieth century.

Microbial fingerprinting would result in a seismic shift in health quality and delivery.

Manipulation and enrichment of select microbial communities — referred to as microbiome engineering – would improve health, rejuvenate organs, enhance character traits and lead to more effective medications.

Microbe-supplemented creams for skin diseases and microbe-fortified nutritional supplements are already being routinely touted as personalized cures.

The tracking of microbes and their metabolites may become a common molecular strategy to identify individuals and even their behaviors.

We are just at the dawn of a health revolution that has the potential to be a societal-game changer.


The University Medical Center Groningen (UMCG) in The Netherlands organizes annual symposia within the compass of medicine and nutrition, as part of its Healthy Ageing program. Previously published proceedings of these symposia have examined the relationship of nutrients with lifelong health and disease [1], with healthy aging [2], with malnutrition and obesity [3], and with nutrient–drug interactions [4].

The 2017 annual meeting at the UMCG focused on the role of the gut microbiome in human health and disease.

The symposium, which brought together experts from academia and industry, examined interactions of prebiotics, probiotics or vitamins with the gut microbiome.

The panel discussed the role of the microbiome on various aspects of healthy and diseased subjects throughout lifespan.

In the context of disease, the symposia focused on two main intestinal conditions: inflammatory bowel disease (IBD), manifesting as Crohn’s disease (CD) or ulcerative colitis (UC); and irritable bowel syndrome (IBS).

Moreover, the various benefits of prebiotics on human health, the microbiome–nutrient interaction and the role of vitamins in promoting the selective growth of microbes in the gut as well as determinants of the development of a healthy microbiome were presented and discussed intensively.

Last but not least, the panel discussed how the brain and the microbiome may affect and control each other’s functions and the implications of such communication for treating or preventing the brain-related functional decline during aging.

It is worth noting that the terms microbiota and microbiome are frequently used interchangeably and this also applies here.

Strictly speaking, however, microbiota is defined as the microbial taxa associated with complex organisms such as humans, whereas microbiome is the catalogue of these microbes and their genes [5].

The totality of data suggests great promise for use of pre- and probiotics in promoting general health and treating human diseases.Go to:

Prebiotic interactions with the microbiome

Dietary prebiotics have been defined as “a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health” [6].

This definition has been subjected to debate as it focuses largely around the need for selective metabolism.

An alternative definition which includes the mechanism of action has been established recently in a consensus statement [7].

The expert panel revised the definition of a prebiotic as “a substrate that is selectively utilized by host microorganisms conferring a health benefit”. This updated definition still requires a selective microbiota-mediated mechanism to be defined as a prebiotic.

Fermentation of dietary prebiotics in the gut involves metabolic cross-feeding where the products of fermentation by one or more bacterial species provide the substrate(s) for other bacterial species (Fig. 1) [8].

This complex cooperative activity of the gut microbiota is essential for good health [89]. Bacterial fermentation of amino acids and proteins, which occurs mainly in the distal colon, generates a range of metabolites, many of which have a toxic potential.

These include hydrogen sulphide, branched-chain fatty acids (BCFAs), phenol, indole, p-cresol, indoxylsulfate, p-cresylsulfate, and ammonia [1012].

Even if also present in the healthy colon, it must be noted, however, that we currently have a very poor understanding of the concentrations of microbial metabolites in the human colon [12].

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Fig. 1
Fermentation and gut microbiota. The figure shows the principle sources of nutrition entering the human colon at the top and the principle metabolic outputs at the bottom. Arrows indicate known cross-feeding relationships between the principle microbial groups present. Metabolites in green boxes are believed to be health-positive while those in red boxes are potentially harmful. Gaseous products are in orange boxes and the most significant intermediate products of metabolism are in blue

Several studies have demonstrated modulation of colonic microbiota by prebiotic inulin or inulin-type fructans. Real-time polymerase chain reaction (PCR) identification of selected bacterial species in the feces of human volunteers after inulin ingestion showed that the prevalence of Faecalibacterium prausnitzii and two Bifidobacterium species, B. adolescentis and B. bifidum, increased significantly [13].

In a placebo-controlled study, dietary inulin-type fructans increased the relative abundance of Bifidobacterium spp. and F. prausnitzii in obese women [14].

In healthy adults with mild constipation, inulin-type fructans increased the relative abundance of Anaerostipes, Bilophila and Bifidobacterium in feces, and reduced the abundance of Bilophila [15].

Differences in selectivity for the fermentation of several carbohydrate substrates (lactulose, galacto-oligosaccharides, sugar beet pectin and apple fiber) were found between the microbiotas from lean and obese healthy subjects using an in vitro model (TIM-2) of the proximal colon, providing the evidence that the composition of the microbiota changes depending on the body mass index (BMI) in humans [16].

Figure 2 summarizes the effects of prebiotics on human health. Several studies have examined the effect of prebiotics on allergic reactions and infections in infancy.

A placebo-controlled randomized trial of infants with a parental history of atopy showed that formula milk supplemented with a prebiotic mixture of galacto-oligosaccharides (GOS) and long chain inulin significantly reduced the incidence of atopic dermatitis. Prebiotic supplements were associated with a significantly increased number of fecal bifidobacteria, but with no significant change in lactobacilli numbers [17].

In this same cohort of infants, the prebiotic supplemented milk significantly reduced the incidence of infectious episodes during the first 6 months of life [18]. In a 2-year follow-up study of this cohort, infants receiving prebiotic supplementation had a significantly lower incidence of allergic manifestations [19].

At 5-year follow-up, infants in the prebiotic supplementation group had a significantly lower incidence of any allergic manifestation and atopic dermatitis compared to the placebo group [20].

The proposed mechanism for this long-lasting effect of prebiotics is immune modulation mediated through changes in the intestinal microbiota [19].

In a three-group randomized intervention study, infants fed prebiotic GOS+inulin supplemented milk had comparable numbers of fecal bifidobacteria and lactobacilli to infants who were breast fed, whereas infants fed standard formula milk had significantly lower numbers of both bacterial genera.

Incidence of gastrointestinal and upper respiratory tract infections was significantly lower in breast fed infants or the ones fed prebiotic supplemented milk compared to standard formula milk. Similarly, allergic reactions to food and milk were significantly higher in the standard formula milk group [21].

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Fig. 2
Effect of prebiotics on gut function and health. The figure indicates likely mechanism of prebiotic action in the gut. In many cases the suggested mechanisms are speculative at the present time. Physiological functions are in purple and health outcomes are in green. Abbreviations: FFAR2/GPR43, free fatty acid receptor 2; FFAR3/GPR41 free fatty acid receptor 3; GLP-1, glucagon-like peptide 1; GLP-2, glucagon-like peptide 2; IFN-γ, interferon gamma; IL-1β, interleukin 1 beta; IL-6, interleukin 6; IL-10, interleukin 10; LPS, lipopolysaccharide; NK, natural killer cells; PYY, peptide YY; Th, T helper cells; TGF-β, transforming growth factor beta; Tr, T regulatory cells; ZO-1 zona occuldens protein 1

A meta-analysis of 26 randomized controlled trials (RCTs) involving 831 healthy adults showed that dietary prebiotic supplementation significantly increased self-reported feelings of satiety compared with placebo [22]. Healthy adults fed an oligofructose-enriched inulin diet experienced lowered hunger and increased satiety rates compared with the placebo, maltodextrin.

The increased feeling of satiety was accompanied by an increase in plasma gut peptide concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY in prebiotic supplemented subjects, which may have contributed to the change in appetite [23], suggesting a potential for use in treating obesity.

Similarly, in obese or overweight children, an oligofructose-enriched inulin diet significantly increased satiety compared with maltodextrin. Prebiotic supplementation led to a significant reduction in energy intake in older (aged 11–12 years), but not younger (aged 7–10 years) children [24] suggesting that prebiotic supplementation can potentially help to regulate energy intake in obese children.

Prebiotics have been used in several studies to treat constipation.

A meta-analysis of RCTs involving 252 subjects (experimental group: n = 144, control group: n = 108) reported that inulin significantly improved bowel function in patients with chronic constipation exhibiting beneficial effects on stool frequency, the Bristol scale of stool consistency, transit time and stool hardness [25].

Following an evidence review the European Food Safety Authority (EFSA) concluded that “chicory inulin contributes to maintenance of normal defecation by increasing stool frequency” [26].

The results were recently confirmed in a randomized, placebo-controlled study showing that chicory inulin was effective in treating healthy subjects with constipation, increasing stool frequency significantly compared with placebo [27].

Additional described effects of prebiotics include reducing toxins produced from protein metabolism in urine (p-cresol and ammonia) [28] and serum (p-cresyl sulphate) [29], and increasing calcium absorption in adolescents [3031].

Prebiotics may also exert beneficial effects on host physiology which are independent of the microbiota as demonstrated by in vitro experiments for GOS. These included modulation of goblet cells to enhance mucosal barrier function [32], a direct protective effect on intestinal barrier function [33], and inhibiting adherence of enteropathogenic Escherichia coli to Caco-2 enterocyte and Hep-2 epithelial cells [34].

An improved understanding of the functional ecology of the gut and a more detailed knowledge of gut metabolites are particularly important for understanding the role of prebiotics on human health.

For some products there is already good evidence on gut health and these findings should be communicated to health care professionals and consumers. On the other side, more studies on the effect of prebiotics on health outcomes in humans are imperative.


Funding: Vasu Appanna receives funding Northern Ontario Heritage Fund . Professor of Biochemistry, Laurentian University, Sudbury, Ontario, Canada.

Source:
The Conversation
Media Contacts: 
Vasu Appanna – The Conversation
Image Source:
The image is credited to Vasu Appanna.

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