Gut Physiology & Microbiota

Digestion and nutrients absorption are routine processes involving several organs' coordination. They are mediated by the secretion of hormones and the enteric nervous system (often designated the “second brain”) and can be substantially impacted by the microbiota.

The gastrointestinal tract (GIT) directly comprises the oral cavity, the pharynx, the oesophagus, the stomach and the small and large intestines. The main function of the tract is the assimilation of nutrients from ingested food that flows through by coordinated motility of the GIT, associated with the appropriate fluid and enzyme solutions. Consequently, the macromolecules in food are gradually digested, and the nutrients liberated are absorbed into the circulatory system. Although digestion and absorption are routine processes, they involve the coordination of several organs, mediated by the secretion of hormones and the enteric nervous system (often designated the “second brain”) (1). The following sequence concisely exemplifies the assimilation of food throughout the GIT, in order to relate the diverse actions and compositions of the microbiota throughout the tract (2):

1. Mastication and Swallowing 

The food breaks in the mouth and forms a bolus suitable to be swallowed, while saliva humidifies and provides enzymes for the initial digestion. Once swallowed, the food bolus takes about 10 seconds to descend into the stomach via the oesophagus.

2. Stomach

Depending on its composition, the bolus remains in the stomach for one to four hours. The organ has three properties that contribute to the digestion. Firstly, stomach mobility mixes and divides the bolus into smaller particles. Secondly, the gastric acid dissolves and denatures proteins into small polypeptides, besides preventing pathogenic organisms present in food to reach the intestines and bloodstream. Thirdly, besides gastric acid, the gastric mucosa produces mucus, that protects the stomach cell wall, pepsinogen, that activates into pepsin when in contact with the gastric acid and breaks proteins, and gastric lipase, that is involved in fat digestion and emulsification (3). Then, the food particles pass through the pyloric sphincter and start to be absorbed by the small intestine. As well as the first part of the small intestine, the stomach contains oxygen and inhospitable physiology, with a less diverse but more aerotolerant and aerobic microbiota. 

3. Small Intestine

Once in the small intestine, the digested food is blended with exocrine secretions containing bicarbonate (HCO3-), that neutralizes the acid from the stomach. The exocrine secretions also contain salts from bile and enzymes from pancreatic and intestinal juices, which are involved in the digestion of proteins, carbohydrates and fat. All the significant absorption of nutrients into the bloodstream occurs in the small intestine, where the food stays around seven to ten hours, advancing through the organ via enteric motility (4). Due to the digestive enzymes and bile of the small intestine, the organ has a less diverse and abundant microbiota than the colon, usually being dominated by species from Streptococcus, Bifidobacterium, Lactobacillus and Enterococcus genera (5). 

4. Large Intestine (Colon)

Finally, the transit reaches the large intestine, starting at the cecum and ending at the sigmoid colon and taking twelve to twenty-four hours to occur. Among several functions, the large intestine is responsible for fluid and electrolyte absorption, and, with the assistance of the microbiota, the fermentation of fibre. The large intestine has the most diverse, abounding and aero-intolerant microbiota of the GIT, with a strong presence of Bacteroidetes and Firmicutes (5,6).

REFERENCES 

1. Collen A. 10% Humanos. 1st ed. Lisboa: Objectiva Editora; 2016. https://www.wook.pt/livro/10-humanos-alanna-collen/17436036.

2. Kibble JD, Halsey CR. Gastrointestinal Physiology. In: Medical Physiology: The Big Picture. McGraw Hill; 2009. https://accessmedicine.mhmedical.com/book.aspx?bookID=1291

3. Armand M, Hamosh M, DiPalma JS, et al. Dietary fat modulates gastric lipase activity in healthy humans. Am J Clin Nutr. 1995;62(1):74-80. doi:10.1093/ajcn/62.1.74

4. Ulleberg EK, Comi I, Holm H, Herud EB, Jacobsen M, Vegarud GE. Human gastrointestinal juices intended for use in in vitro digestion models. Food Dig. 2011;2(1-3):52-61. doi:10.1007/s13228-011-0015-4

5. Mailhe M, Ricaboni D, Vitton V, et al. Repertoire of the gut microbiota from stomach to colon using culturomics and next-generation sequencing. BMC Microbiol. 2018. doi:10.1186/s12866-018-1304-7

6. Hillman ET, Lu H, Yao T, Nakatsu CH. Microbial ecology along the gastrointestinal tract. Microbes Environ. 2017;32(4):300-313. doi:10.1264/jsme2.ME17017

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Role of the Normal Gastrointestinal (Gut) Microbiota

The gastrointestinal microbiota is involved in multiple aspects of our metabolism, being moderately responsible for our health equilibrium.

Role of the Normal Gastrointestinal (Gut) Microbiota

At the beginning of the century, the significance of the human forgotten organ, the gut microbiota, started to be widely recognized and studied. Nowadays, it is well established that a healthy gastrointestinal tract (GIT) microbiota is moderately responsible for the health of the host (1). Among several roles, the GIT microbiota is associated with the following functions: 

1. Metabolic 

The GIT microbiota is involved in multiple aspects of our metabolism, for example, by producing essential nutrients (such as vitamins K2 and B12, folate, amino acids and fatty acids) and extracting energy from fibre. In fact, vegetables, nuts and fruits have a fair amount of non-digestible fibre (dietary fibre) that reaches the large intestine mainly intact. Once there, the microbiota can take advantage of dietary fibre and generate energy from it, producing waste products such as short-chain fatty acids. Those acids can be used as an energy source by GIT cells and help to maintain a healthy pH, which inhibits the growth of some pathogens. For instance, butyrate is one of the most relevant short-chain fatty acid produced by the intestinal microbiota. Besides being an energy source for the colon, it has anti-inflammatory and immunomodulatory properties (2). 

Figure 1 — A fibre-rich versus a fibre-deprived gut microbiota (10).

2. Structural and Protective

The GIT prevents potential pathogenic microorganisms from adhering to its cells, as it establishes an extensive surface coating in the epithelium and may produce antimicrobial compounds (such as bacteriocins and acids). Additionally, the immune cells of the GIT secrets roughly 60% of the human body immunoglobulins, in the vast gut-associated lymphoid tissue (GALT), that has a strong relationship with the microbiota (3,4). Although countless beneficial interactions have been established between GIT immune cells and GIT microbiota, the majority may remain uncertain or unknown.

3. Maturation of Innate and Adaptive Immune Responses 

It is also very significant to help the immune system distinguishing commensal from undesirable microorganisms (5). Commensal GIT microbes can interact with the immune system and induce regulatory T cells, that balances the host Th1 and Th2 immune responses, which dysregulation may lead to autoimmune and atopic diseases, respectively (6,7). Therefore, a healthy GIT microbiota may play a significant role in diminishing the prevalence and symptomatology of autoimmune disorders and allergies. 

4. Physical and Psychological Health 

In the last decade, the GIT microbiota has been closely associated with the global health of its host. For example, multiple cases of autism have been related to disturbs of the microbiota, principally due to a prolongated intake of antibiotics in the first years of life and Clostridium enteric infections (8). The GIT microbiota has also been linked to variation in moods and emotions by excreting neurotransmitters into the bloodstream, such as noradrenaline and serotonin by certain strains of Escherichia coli. The microbiota-gut-brain axis is one of the most complex and least know interactions to date and can be closely related to mood disorders, which affects 10% of the world’s population. Therefore, the GIT microbiota emerges as a potential therapeutic and diagnose target to treat such disorders in the future (9).

REFERENCES 

1. O’Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7(7):688-693. doi:10.1038/sj.embor.7400731 
2. Liu H, Wang J, He T, et al. Butyrate: A double-edged sword for health? Adv Nutr. 2018;9(1):21- 29. doi:10.1093/advances/nmx009 
3. Arrazuria R, Pérez V, Molina E, Juste RA, Khafipour E, Elguezabal N. Diet induced changes in the microbiota and cell composition of rabbit gut associated lymphoid tissue (GALT). Sci Rep. 2018;8:14103. doi:10.1038/s41598-018-32484-1 
4. Brandtzaeg P, Halstensen TS, Kett K, et al. Immunobiology and immunopathology of human gut mucosa: Humoral immunity and intraepithelial lymphocytes. Gastroenterology. 1989;97:1562-1584. doi:10.1016/0016-5085(89)90406-X 
5. Montalto M, D’Onofrio F, Gallo A, Cazzato A, Gasbarrini G. Intestinal microbiota and its functions. Dig Liver Dis Suppl. 2009;3(2):30-34. doi:10.1016/S1594-5804(09)60016-4 
6. Azad MB, Kozyrskyj AL. Perinatal programming of asthma: The role of gut microbiota. Clin Dev Immunol. 2012;2012:932072. doi:10.1155/2012/932072 
7. Skapenko A, Leipe J, Lipsky PE, Schulze-Koops H. The role of the T cell in autoimmune inflammation. Arthritis Res Ther. 2005;7(Suppl 2):S4-14. doi:10.1186/ar1505 
8. Collen A. 10% Humanos. 1st ed. Lisboa: Objectiva Editora; 2016. https://www.wook.pt/livro/10-humanos-alanna-collen/17436036. 
9. Huang TT, Lai JB, Du YL, Xu Y, Ruan LM, Hu SH. Current understanding of gut microbiota in mood disorders: An update of human studies. Front Genet. 2019;10:98. doi:10.3389/fgene.2019.00098
10. Desai MS, Seekatz AM, Koropatkin NM, et al. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell. 2016 Nov 17;167(5):1339-1353.e21. doi: 10.1016/j.cell.2016.10.043. PMID: 27863247; PMCID: PMC5131798

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