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The impact of gut microbiota on the host's endocrine function.
The gut microbiome is considered an organ that helps regulate host metabolism. With the elucidation of the relationship between the gut microbiome and specific diseases, many studies have decoded how gut bacteria interact with host cells and ultimately affect the molecular mechanisms of metabolism. Metagenomic and metabolomic analyses have both contributed to the discovery of bacterial-derived metabolites that act on host cells.
Gut Microbiome Composition
According to recent estimates, a person of normal weight has about 3.9×10^13 bacteria in their gut, primarily located in the colon, with a ratio of bacteria to human cells of about 1:1. In 2014, a gene catalog expressing the human microbiome was created by metagenomic sequencing of fecal samples from 1,070 individuals across three continents (America, Asia, and Europe); this catalog contains approximately 10 million bacterial genes, which is 500 times the number of genes in the human genome. In the same study, it was calculated that each fecal sample contains an average of 762,655 gut bacterial genes, meaning this gene count is 38 times greater than that of the human genome.
What different metabolites do gut bacteria produce?
Short-chain fatty acids
The human gastrointestinal tract is specialized for the digestion and absorption of various nutrients present in food. In fact, almost all fats in a meal are absorbed, with only a very small portion (<5 g/d) escaping digestion and ultimately reaching the colon to be excreted. This complex process involves many factors, including bile acids and different lipases, and fatty acids are ultimately actively transported into intestinal epithelial cells. The upper gastrointestinal tract is also very effective in digesting and absorbing monosaccharides and most amino acids derived from the digestion of proteins in the diet.
In contrast, the human gut cannot digest all the different types of carbohydrates present in our diet. The chemical properties of these fibers vary depending on their source (e.g., grains, fruits, and vegetables). Therefore, a large amount of carbohydrates escape digestion in the upper gastrointestinal tract and become what is known as dietary fiber. As a result, dietary fiber is used as an energy source by specific gut bacteria. Various enzymatic mechanisms of some bacteria help metabolize these indigestible carbohydrates into different molecules, such as short-chain fatty acids (SCFAs) (e.g., acetate, butyrate, and propionate).
Neurotransmitters
Gut microbes are also capable of synthesizing 'classical' neurotransmitters derived from amino acids and gaseous neurotransmitters. These neurotransmitters have local effects on gut physiology (e.g., motility, gut hormone release) through connections between the gut nervous system and the brain, and they influence 'central' effects (e.g., cognition, behavior).
First, gut microbes can secrete histamine. Histamine is a monoamine synthesized from the decarboxylation of the amino acid histidine. Recently, research by Barcik et al. showed that the number of histamine-secreting microbes in the gut of asthma patients is significantly increased, indicating that bacterial histamine may be involved in the regulation of gut immunity.
Hata et al. found that bacteria can produce free serotonin by enzymatically cleaving glucuronic acid-bound serotonin. Germ-free mice exhibited reduced monoamine activity associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, suggesting that the gut microbiome can influence systems related to the psychopathology of depression. To support this finding, the use of probiotic Bifidobacterium infantis in conventional mice increased circulating levels of tryptophan, reduced the ratio of kynurenine to tryptophan, and decreased products of serotonin breakdown in the brain, indicating that this probiotic has antidepressant effects.
Summary
① The number of genes in the human gut microbiome is 38 times that of human genes, and its metabolic capacity should not be underestimated;
② Products of the gut microbiome, such as short-chain fatty acids and amino acid metabolites, can participate in regulating host energy, blood sugar, and inflammation through various pathways (e.g., gut hormone GLP-1);
③ The gut microbiome can regulate bioactive lipids and specific neurotransmitters (e.g., γ-aminobutyric acid, serotonin) in the endocannabinoid system.
④ It is expected that various microbial products capable of regulating host physiological health will be discovered in the future, some of which may become therapeutic agents.
References:
The Gut Microbiome Influences Host Endocrine Functions
https://doi.org/10.1210/er.2018-00280
Chuangyuan Biotechnology
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