The human body is colonized with thousands of diverse microbes including bacteria, archaea, eukaryotes, and viruses. The microorganisms are spread across multiple body sites, including the gut, mouth, vagina and skin. Each body site is characterized by different organisms with different functional roles. The gut microbiome is the most studied human ecosystem to date and is primarily comprised of bacteria and bacteriophages (viruses). Research over the last decade has extensively expanded our understanding of its composition and has sheet light on its many important functions for human health.
The composition of the gut microbiome
The human gut microbiome includes more than 1,000 different bacterial species; however, a few different phyla dominate, namely bacteria from four phyla: Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria. Of these four, Bacteroidetes and Firmicutes are the most abundant phyla in a normal healthy western gut. A handful of taxa generally dominant at the lower taxonomic levels, however the composition of these microbes varies considerably, leading to strong inter-individual variation. In addition to the few dominant genera, many less abundant taxa are common, including Akkermansia, Bifidobacterium and Escherichia. Research has shown that the abundance of a bacteria not necessarily reflect its functional importance, as variations in both common and rare taxa increasingly are found to associate with host health and function.
Good or bad?
Labeling specific bacteria as good or bad for the host is difficult and perhaps not achievable above strain-level because of the high intra-species functional variation. Variation at the strain level can determine if a taxon is detrimental or harmless, as is seen for Escherichia, which is commonly found in the gut of humans with good health where it aids in metabolism. But based on gene-based variation, by encoding toxins, strains can be pathogenic. The ability of bacteria to perform horizontal gene transfer – the transfer of a gene between living bacterial cells – introduce intra-strain variation that is not captured by marker-gene based taxonomical analysis. However, it is an important source of functional variation as seen with the ability of bacteria to transfer antibiotic resistance genes.
Pro- and prebiotics
The production of acetate and lactate during carbohydrate fermentation is among the many important functions belonging to the gut microbiome, including strains of the Bifidobacterium clade. The role of the gut microbiome for fermenting carbohydrates and in turn production of short-chain fatty acids is a key function for maintaining gut health. As a consequence, lactic acid bacteria including Bifidobacteria, are considered probiotics – beneficial bacteria.
There are a large number of pre- and probiotic products on the market, usually as additives to yoghurts or taken as food supplements. Products containing living microorganisms, for example Lactobacillus acidophilus and Saccharomyces boulardii, must have a beneficial effect to human health to be named a probiotic. While probiotics hold a great potential for modifying the human microbiome in a positive way, much work still remain before we can fully harvest the benefits of probiotics. Numerous placebo-controlled studies have been performed for various indications, and while some show indications for a positive effect, others have not shown convincing results, such as a preventive measure for travel diarrhea. Prebiotics are not live microbes, but a substrate that is used by host microbes to bestow a health benefit. Although all compounds considered prebiotics are microbiota accessible carbohydrates or fermentable dietary fiber, the reverse is not true. The prebiotic concept is an area of current debate.
Factors shaping the gut microbiome
The gut microbiome is shaped by multiple factors, including a complex interaction between its microbial members, the host immune system and nutritional habits. Shaping factors include both those endogenous (immune system, bile acids, hormones) and exogenous (diet, physical activity, medication) to the host. Together these constitute the environment in which the gut microbiome exists and must navigate. Active research is ongoing to elucidate the exact factors shaping the microbiome, including an interesting evaluation of the role of competition versus cooperation for shaping the microbiome, a field led by professor Kevin Foster.
The role of the gut microbiome
The gut microbiome plays an essential role for the health of its host, humans as well as animals. Its key functions relate to metabolism, immune system education and regulation, and protection against pathogen invasion. If not for the gut microbiome the human body would lack a number of nutrients, including vitamins and amino acids. Among the essential roles of the gut microbiome is the capacity for fermentation of non-digestible fibers. These fibers are nutrients for a group of that produce short chain fatty acids (SCFAs). The most important SCFAs produced are acetate, propionate, and butyrate, of which acetate is the most abundant. Butyrate is an important energy source for the cells that make up the inner lining of the human colon (colonocytes), and lack of SCFA is believed to play a key role in many microbiome-related issues such as leaky gut and local inflammation. Butyrate has been linked to a number of important functions including the ability to induce apoptosis of colon cancer cells, and activation of intestinal gluconeogenesis that is relevant for energy balance and diabetes. Also, propionate is important for glucose homeostasis as it regulates gluconeogenesis in the liver and is involved in satiety signaling. Finally, acetate plays important roles for the regulation of metabolism in extra-intestinal tissues including cholesterol metabolism and lipogenesis.
The microbiota in the human gut colonize all available niches and thereby protect the host by competing for the space with potentially pathogenic microorganisms. A balanced community is important for keeping pathogens at bay, which is a key hypothesis as to why fecal transplantations are so effective at treating infections with Clostridium difficile. Beyond the space-occupying defense mechanism, the microbiome helps to defend the host by contributing to the education of the immune system. The intestine is rich in immune cells and these cells actively interact with the microorganisms to promote immune tolerance. A lack of beneficial bacteria or dysbiosis is thought to promote inflammation by imposing changes to the composition of microbial components that inter the body, by damaging the intestinal epithelial causing a leaky gut. Bacterial components such as lipopolysaccharide (LPS) can leave the intestine and increased levels or changes to the types of LPS that the immune system encounter can cause local and systemic inflammation.
In addition to the microbiomes many roles for normal human function, it has also been extensively related to the development and progression of many diseases. Over the last years there has been found a direct link between the gut microbiome and mental health. Research show that the intestinal microbiota can affect the brain’s normal function and development. Comparison of children with and without ADHD or autism have found that patients with these conditions have a gut bacterial composition that is different from patients without. But also, cancers, inflammatory and autoimmune conditions and metabolic diseases such as diabetes has been linked to the gut microbiome. And we have seen an increasing interest in the ability of the gut microbiome to affect drug metabolism thereby affecting the amount of active drug made available to the host.
References and suggested readings
- Valdes et al., (2018). Role of the gut microbiota in nutrition and health. Doi: https://doi.org/10.1136/bmj.k2179
- Hughes RL. (2020). A Review of the Role of the Gut Microbiome in Personalized Sports Nutrition. Doi: https://doi.org/10.3389/fnut.2019.00191
- Mohajeri et al., (2018). The role of the microbiome for human health: from basic science to clinical applications. Doi: 1007/s00394-018-1703-4
- Lloyd-Price et. al., (2016). The healthy human microbiome. Doi: 10.1186/s13073-016-0307-y
- Falony et al., (2016). Population-level analysis of gut microbiome variation. Doi: 10.1126/science.aad3503
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