The evolution of bacteria in the human microbiome

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Beneficial bacteria in the gut microbiome use different means to transmit from one person to another which impacts their abundance in the gut and the functions they provide, new research has found.

This novel research, by scientists at the Wellcome Sanger Institute, used genetic sequencing to shed new light on the evolution, colonization and transmission of gut bacteria, which play a large role in human health.

The study, published today in Genome Biology, provides a deeper understanding of the evolution of bacteria in the human microbiome. It could also inform the development of microbiome-based therapeutics where key bacteria could be selected to treat different intestinal-associated illnesses.

Humans are populated by an extremely large amount of microorganisms, called a microbiome, which include bacteria, viruses, archaea and fungi.

Beneficial bacteria in the body roughly match human cells one to one and in the gut, this collection of bacteria has been found to play an important role in human health. The makeup of the gut microbiome affects the immune system, prevents infections and supports the body by breaking down some carbohydrates that human cells cannot do alone.

In order for bacterial species in the gut to survive, they have to be able to transmit from one person to another. Gut bacteria are mainly anaerobic, meaning they cannot survive in oxygen. To spread, some produce spores, which are sometimes likened to seeds and can lie dormant until they encounter the right conditions to grow.

This research, from the Wellcome Sanger Institute, investigated the group of bacteria known as the Firmicutes, which are dominant in the human microbiome and produce spores. The researchers analyzed the genomes of 1,358 Firmicutes and tracked the evolution of certain characteristics, including spore production.

They observed that gut bacteria that form spores were found at lower abundances in the gut, and had larger genomes compared to those that had lost the ability to produce spores (sporulate). Within their genomes, they also had more genes associated with carbohydrate metabolism and vitamin biosynthesis, which suggests that they have important metabolic functions.

Firmicutes bacteria that could no longer form spores had smaller genomes, but were present at higher abundances in the gut and had a more specialized metabolism based on genome analysis. They were also less prevalent in the general population, meaning they were found in a smaller number of individuals, suggesting loss of sporulation limits their ability to transmit widely.

Smaller genomes and more specialized metabolism indicate that bacteria that have lost the ability to sporulate are becoming more adapted to their human host which could allow them to colonize to higher levels in the gut. On the other hand, bacteria that still produce spores appear less adapted to humans based on their larger genomes which could explain why they are not as abundant in the gut.

These differences show that that transmission is an important process that shapes the evolution of gut bacteria and further research is now needed to continue to learn more about the link between transmission of gut bacteria and the roles they play in human health.

Understanding these processes could help inform therapeutics, such as investigating whether specific bacteria could be given to people based on their ability to colonize and how the differing metabolism of these bacteria could impact health conditions and treatments.

Dr. Hilary Browne, first author and Staff Scientist at the Wellcome Sanger Institute, said: “Even though transmission of gut bacteria between humans is essential for their survival, the genetic and biological features of the bacteria that allows them to do this, is still poorly understood.

This research starts to unravel some of this mystery by analyzing the genomes and finding that the ability of bacteria to produce spores has been lost multiple times, impacting their evolution and function. It is necessary to continue looking at the genetic detail of the microbiome to help understand the roles of specific bacteria, and how lacking these might impact human health.”

Dr. Trevor Lawley, senior author and Senior Group Leader at the Wellcome Sanger Institute, said: “The microbiome plays an essential role in human health and development, and influences a wide range of physiological functions in the body.

Understanding more about the bacteria that inhabit us and how they are adapted to living in humans through their metabolism will be important for the development of new therapeutics and diagnostics for microbiome-mediated diseases.”


The role of human microbiome in viral transmission

The implications of the microbiome in infectious (Hanada et al., 2018) and non-infectious disease (Cryan et al., 2020) has been well documented. The theory of sterile lungs has been shifted to “lung microbiome”, the resident microflora of the respiratory system (Dickson et al., 2016), however contagion specific fingerprint of lung microbiome remains to be fully established. The development and establishment of lung microbiome and lung-gut-axis play a critical role in respiratory diseases (Unger and Bogaert, 2017; Enaud et al., 2020).

The usefulness of the nose/throat microbiome is being utilized in the prediction of vulnerability to influenza and also modulation of the microbiome can lower the chances of infection (Fanos et al., 2020). Tsang et al. (2019) observed that increased abundance of Streptococcus spp. reduced the vulnerability to influenza A(H3N2) and influenza B infection by 48 % and 25 % respectively, whereas a ten times greater abundance of Prevotella salivae reduced the vulnerability to influenza virus A(H3N2) by 63 % and increased the vulnerability to influenza B infection by 83 %.

SARS-CoV-2 gain access to the cell via the angiotensin-converting enzyme 2 (ACE-2) receptor (Yan et al., 2020; Zhou et al., 2020). The single-cell RNA sequencing (scRNA-seq) revealed that ACE-2 is present in various organs where they are located on specific cell types such as ileum and esophagus epithelial cells, type II alveolar cells (AT2) in lungs, proximal tubule cells in the kidney, myocardial cells and bladder urothelial cells, which indicates the vulnerability of these organs to COVID-19 infection.

Individuals have reported certain clinical symptoms such as acute cardiac injury and kidney failure along with common symptoms like dyspnea and diarrhea which could be attributed to the invasion of SARS-CoV-2 into the heart and kidney along with lung, upper respiratory tract and ileum (Zou et al., 2020).

The microbiome present in the lung tissue of patients who were deceased due to COVID-19 was studied and results reveal that the most predominant bacterial members were of the genera Acinetobacter, Burkholderia, Chryseobacterium, Sphingobium, Brevundimonas and Enterobacteriacea; and the fungal members included Aspergillus spp., Issatchenkia spp., Candida spp., Alternaria spp., and Cladosporium spp., which are well known opportunistic invasive pathogens in immunocompromised patients. Hence, a combination of bacterial and fungal infections was observed (Fan et al., 2020).

ACE-2 receptors are also present in oral cells, mainly in tongue epithelial cells as per the recent report (Xu et al., 2020), which indicates that SARS-CoV-2 could interact with the oral microbiome, hence causing co-infection between the oral microbiome and SARS-CoV-2 in the lungs of the infected individuals (Bao et al., 2020). Capnocytophaga, Veillonella (Chen et al., 2020) and potential pathogens such as Pseudomonas, Acinetobacter, Escherichia and Streptococcus were present in the Bronchoalveolar lavage fluid (BALF) of COVID-19 patients (Ren et al., 2020).

The SARS-CoV-2 could hinder the nutrient absorption by binding to ACE-2 receptors which leads to gastroenteritis-related symptoms and disturbance of gut homeostasis (Gu et al., 2020). The individuals suffering from respiratory illness also undergo gut dysbiosis which indicates the presence of gut-lung crosstalk (Fanos et al., 2020). The gut-lung axis is bidirectional because the microbial metabolites and endotoxins produced in the gut reach the lungs via blood, also any infection or inflammation in the lungs affects the gut microbiome (Dumas et al., 2018; Dhar and Mohanty, 2020).

The action of ACE-2, present on the surface of the lumen of the intestine is known to be influenced by the gut microbial community in COVID-19 (Yan et al., 2020). Hence, it indicates the impact of SARS-CoV-2 infection on the gut microbiome. Also, various studies have revealed the alteration in the gut microbiome during respiratory infections (Dhar and Mohanty, 2020; Groves et al., 2020).

Viral as well as the cytokine storm‐driven variations enhance the gut permeability and lead to dysbiosis, which reduces the amounts of short‐chain fatty acid (SCFAs) such as butyrate, and carries lipopolysaccharide (LPS) into the circulation (Anderson and Reiter, 2020). The ‘colonization resistance’ strategy used by the host microbiome prevents the colonization of pathogens whereby the beneficial microbes occupy the pathogen’s niche or the mucosal entry points specific to the pathogens and also initiating the innate immune response (Thaiss et al., 2016).

And few viruses can take over and manipulate the signaling interactions such as Lipopolysaccharide-Toll-like receptor 4 (LPS-TLR4) signaling between the microbiome and immune system, hence benefiting their own proliferation and spread (Domínguez-Díaz et al., 2019).

Enteric viruses like Poliovirus, Norovirus and mouse mammary tumor virus have been found to utilize the microbial components like lipopolysaccharides to evade the host immune response (Kane et al., 2011; Robinson et al., 2014; Berger and Mainou, 2018); and the virion thermostability of reovirus was enhanced due to its interaction with bacterial cells (Berger et al., 2017; Berger and Mainou, 2018).

A study revealed that allogeneic hematopoietic cell transplantation (HCT) recipients having higher loads of butyrate-synthesizing bacteria were at five times lower risk to develop viral lower respiratory tract infection (LRTI). Hence, a higher abundance of butyrate-synthesizing bacteria is associated with higher resistance against LRTI in allo−HCT recipients (Haak et al., 2018).

The gut microbiome composition of individuals infected with COVID-19 showed a significant reduction in bacterial diversity with an increase in the abundance of opportunistic pathogens like Rothia, Streptococcus, Actinomyces and Veillonella, and a reduction in beneficial microbial partners when compared with the healthy control group (Gu et al., 2020). A study revealed that individuals infected with COVID-19 had persistent shifts in the fecal microbiome when compared with the healthy control group which was associated with the fecal levels of SARS-CoV-2 and also the COVID-19 severity.

In severe cases of COVID-19, opportunitistic pathogens like Coprobacillus, Clostridium hathewayi and Clostridium ramosum were observed. The disease severity was inversely proportional to the abundance of an anti-inflammatory bacterium, Faecalibacterium prausnitzii and also few other beneficial bacteria like Eubacterium ventriosum, Faecalibacterium prausnitzii, Roseburia, Lachnospiraceae (Zuo et al., 2020). Hence, the modulation of the gut microbiome might lower the disease severity.

A study in China reported that few patients with COVID-19 also revealed gut microbial dysbiosis with a reduced abundance of Lactobacillus and Bifidobacterium (Mak et al., 2020; Xu et al., 2020). Changes in gut virome due to viral infections and their impact on liver health could provide better insights into the treatment of viral hepatic diseases (Scarpellini et al., 2020). Further investigation is required to provide a better understanding of the effect of the mutation in SARS-CoV-2 on shift in the microbiome due to zoonotic transmission.

Various factors influence the lung microbiome such as microbial composition, lifestyle, smoking, diet, use of chemotherapeutics, and the host immune response (Toraldo and Conte, 2019), and the COVID-19 severity is influenced by old age (Chen et al., 2020), cardiovascular disease (CVD), diabetes mellitus, hypertension, respiratory disorders, etc. Also, recently obesity has been linked to severe COVID-19. Obesity is also associated with dysbiosis and poor immune response against viral infections (Alberca et al., 2020).

A high-fat and fructose-rich diet which is mainly associated with obesity (Namekawa et al., 2017), also reduces the ACE-2 levels significantly (Bundalo et al., 2016). The consumption of higher amounts of processed food increases sodium intake which leads to higher oxidative stress and reduced ACE-2 expression in kidneys (Bernardi et al., 2012), along with hypertension and CVD (Hendriksen et al., 2014). Lowered expression of ACE-2 is closely linked with higher COVID-19 severity (Alghatrif et al., 2020).

Nutritional interventions and the use of probiotics could prove beneficial in boosting the immunity of the host. Modulation and manipulation of microbiome via probiotics, prebiotics and high-fiber diet consumption may lower inflammation and dysbiosis by maintaining a healthy gut microbiome and also boosts the immune response (Toraldo and Conte, 2019).

The beneficial activity of probiotics on pro-inflammatory and immune-regulatory cytokines leads to a reduction in the virus load, acute respiratory distress syndrome (ARDS) and also lowers the tissue damage caused by the cytokine storm which occurs in individuals with severe COVID-19 (Baud et al., 2020).

Supplementation of combined prebiotics, probiotics, synbiotics and nutrition-enriched plant bioactives modify the bacterial composition and can protect against viral infections of the respiratory tract to some extent (Shinde et al., 2020). Due to various positive aspects of probiotics, such as anti-viral action, gut microbiome rebiosis, anti-inflammatory activity, easy availability, ease of administration, safety, and affordable nature, it could prove helpful in the treatment of COVID-19 (Angurana and Bansal, 2020).

Hence, it is proposed that well documented probiotic strains should be considered and used for clinical trials to treat COVID-19 (Giannoni et al., 2020). In the coming days, the use of metabolomics could decipher the furtive dialects between the microbiome and its host (Fanos et al., 2020). Therefore, microbiome-mediated treatment strategies could be implemented to boost immunity, and also further studies in this field could support the present treatment strategies to some extent.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524452/


More information: Host adaptation in gut Firmicutes is associated with sporulation loss and altered transmission cycle, Genome Biology (2021). DOI: 10.1186/s13059-021-02428-6
Revised Estimates for the number of human and bacteria cells in the body. PLoS Bio (2016). DOI: 10.1371/journal.pbio.1002533

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