Edited by Eldrian Tho.
In humans, apart from the trillion of body cells, there are also other microorganisms inhabiting different parts of the human body, collectively termed as microbiota. Gastrointestinal (GI) tract is one of the body parts that is abundant with microorganisms, in which it is estimated that there are more than 10¹⁴ of microorganisms present in human GI tract⁽¹⁾. As defined by Nobel Prize in Physiology or Medicine laureate Joshua Lederberg, the totality of microorganisms including bacteria, viruses, protozoa, fungi and their collective genetic material present in the GI tract is termed as gut microbiome⁽²⁾.
In general, gut microbiota comprises both commensal and pathogenic microorganisms⁽²⁾. The main components of gut microbiota include bacteria, fungi, viruses (mainly intestinal bacteriophage), archaea, protozoa and other Eukarya such as Blastocystis and Amoebozoa⁽³⁾. Among the gut microbiota, bacteria are the most predominant in which it is predicted that there are more than 1,100 species of bacteria which account for more than 1kg of weight present in the human GI tract⁽³⁾. Common phyla of gut microbiota include Bacteroides, Firmicutes, Actinobacteria and Proteobacteria⁽³⁾. Depending on the condition of different parts of the GI tract, the composition of bacteria varies⁽⁴⁾. For example, in stomach with high acidity, there is only presence of few bacteria such as acid-tolerant lactobacilli and Helicobacter pylori while the number of bacteria increases down the GI tract in which large intestine is believed to be colonized by 10¹¹/ml of bacteria, predominantly by anaerobes⁽⁴⁾. In comparison to bacterial communities, there is a lower diversity of mycobiome⁽⁵⁾. The human gut mycobiome is generally dominated by yeast genera such as Saccharomyces, Malassezia and Candida⁽⁵⁾. In terms of mycobiome, research about it is still limited and more studies are to be done to further explain its significance.
Truth to be told, gut microbiome is associated with a wide range of physiological functions in our body. First and foremost, gut microbiome is closely related with nutrient metabolism⁽⁶⁾. Colonic organisms such as Bacteroides, Roseburia, Bifidobacterium, Fecalibacterium and Enterobacteria are responsible to ferment carbohydrate that escaped proximal digestion and indigestible oligosaccharide into short-chain fatty acid (SCFA) which will be involved in regulation of various important cellular processes such as gene expression, chemotaxis, differentiation, proliferation and apoptosis⁽¹⁾. Besides carbohydrates, gut microbiota are found to be augmenting the efficiency of lipid and protein metabolizing machinery⁽¹⁾. Gut microbiota also play an important role in de novo synthesis of essential vitamins in the human body(1). For instance, production of vitamin B12 is dependent on lactic acid bacteria while Bifidobacteria are responsible for the production of folate⁽¹⁾. Synthesis of other vitamins such as vitamin K, riboflavin, biotin, nicotinic acid, pantothenic acid etc. also depends on different gut microbiota⁽¹⁾. According to Jandhyala et al. (2015), gut microbiota are accountable for breakdown of polyphenols in diet by biotransforming polyphenols into active compounds that will provide antimicrobial and other metabolic actions after removing the sugar moiety⁽⁶⁾. In terms of metabolism, gut microbiota is found to be linked to xenobiotic and drug metabolism via mechanism such as reductive metabolism, hydrolytic reaction, demethylation, deamination, dihydroxylation, diacylation, decarboxylation and oxidation⁽⁷⁾.
On the other hand, gut microbiota are involved in the immune system of the host. As suggested by Jandhyala et al. (2015), gut microbiota will provide antimicrobial protection to the host either by competing for attachment sites and nutrient sources with invading pathogen or producing antimicrobial proteins such as cathelicidin, C-type lectin and prodefensin⁽⁶⁾. At the same time, the properties, especially the thickness and composition of the mucus layer in the intestine which acts as a protective layer against pathogen invasion is also determined by specific commensal bacteria⁽⁸⁾. Moreover, commensal bacteria in the gut are involved in induction of mucosal secretion IgA (sIgA) which plays an important role in providing immune protection against pathogens⁽¹⁾. Other than that, the gut microbiota is found to be associated with immunomodulation by mediating the induction of TH17 and Tᵣₑg cells in the intestinal environment⁽⁶⁾⁽⁹⁾.
Surprisingly, there is evidence suggesting that the effect of gut microbiota is far more than only the gastrointestinal environment, but also the central nervous system (CNS), which is termed as gut-brain axis⁽⁸⁾. The concept of gut-brain axis suggested that the interaction between the gut microbiome and the CNS is bi-directional in which both of them will continuously affect each other in some ways. For instance, the CNS is able to affect the gut microbiome by regulating the satiety which will directly impact the nutrient availability and composition of gut microbiota while the commensal gut microbiome can affect the CNS by impacting the autoreactivity of peripheral immune cells to CNS⁽⁸⁾. However, the evidence regarding the gut-brain axis nowadays is mostly limited to animal models. Evidence supporting the effects of gut microbiota on the brain and behavior include the increased anxiety-like behavior in mice due to dysbiosis⁽¹⁰⁾. In terms of humans, researchers are still working on to accumulate more epidemiological evidence to relate microbiome with CNS pathologies such as multiple sclerosis, depression and anxiety as well as to elucidate the mechanisms behind⁽⁸⁾.
Obviously, the gut microbiome is closely related to the body's physiological functions. To better understand the gut microbiome, there are studies conducted to investigate the factors that could influence the composition of the gut microbiota. According to a population-level level analysis on gut microbiome variation published in 2016, factors correlated with it range from medication, blood parameters, bowel habit, health status, lifestyle and many more with different significance⁽¹¹⁾.
Among the covariates investigated, medication shows the strongest explanatory value on the gut microbiome variation⁽¹¹⁾. Among the medications shortlisted in the study, intake of antibiotics, especially broad-spectrum antibiotics such as the β-lactams are found to have rapid and persistent effects on the gut microbiome as the bacterial diversity will be rapidly reduced⁽¹¹⁾⁽¹²⁾. A severe reduction in the commensal bacterial community will ultimately result in microbial dysbiosis which is believed to be a predisposing factor to inflammatory bowel disease⁽¹²⁾. The effect is especially obvious in the case of early antibiotic exposure in neonates⁽¹²⁾.
One of the most interesting factors which is currently being actively explored would be the link between diet and the gut microbiome variation as dietary choice is rather easier to be manipulated. In a study of human gut microbiome by using dietary inventories and 16S ribosomal DNA sequencing, a long-term diet of protein and animal fat is found to be associated with Bacteroides whereas a long-term diet of carbohydrate is found to be associated with Prevotella⁽¹³⁾. On the other hand, there are studies showing that an animal-based diet is linked to the increase of bile-tolerant microorganisms and outgrowth of microorganisms capable of triggering inflammatory bowel disease as well as decrease of Firmicutes which is responsible for dietary plant polysaccharides metabolism⁽¹⁴⁾. Another interesting finding is that yoghurt consumption is associated with increased number of lactic acid bacteria in the GI tract which are able to modify the intestinal environment by increasing tight junctions in the gut epithelium and decreasing potentially harmful enzymes produced by other resident bacteria⁽¹²⁾.
In summary, the relationship between environmental factors, the gut microbiome and human overall health remains a clinically relevant and interesting area to explore and research on. In parallel with the advancement in sequencing technology and bioinformatics, it is believed that more information regarding the gut microbiome could be revealed in the future and this potentially brings new breakthroughs in the healthcare industry.
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