The digestive canal is an apparatus which allows the communication between the interior parts of the organism and the external environment. For this reason, our body is “protected” from direct contact with intestinal lumen content thanks to the intestinal barrier, consisting of mucosal epithelium, MALT (mucosal associated lymphoid tissue) and intestinal microflora.
After birth, the intestinal trait is progressively colonized by a multitude of beneficial bacteria or potentially pathogenic and other microorganisms- viruses, protozoa, fungi- which, co-living together, perform important functions for the organism and for microbial ecosystem itself. The set of all microorganisms colonizing the intestinal trait is known as microbiota: once considered as host of our body, now instead it is recognized as the big “temple” which hosts us, because the number of microorganisms which populate it is much higher than the number of our cells.
This big living population feeds on what we don’t eat, it communicates through enteric nerve cells (“second brain”) with the “first brain” and it regulates, modulating the immune system (also present at enteric level), our general health status through a favorable cohabitation.
It is no coincidence that bacteria, immune system and enteric brain all develop at the same time and they establish a vital and mutual communication during the first thousand days of the newborn.
Intestinal microbiota is a complex and large bacteria community belonging to more than 1000 species, classified in 11 phyla; it is an organ formed by trillion (so, thousands of billions) of bacterial cells, weighting almost 2 kilos. The dominant intestinal microbic phyla are: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia.
The composition of this commensal community changes over a lifetime and it is very sensitive to nutritional changes, environmental factors (i.e. climate or lifestyle), pathologies (i.e. gastrointestinal infections) and pharmacological (i.e. antibiotics use).
Firmicutes and Bacteroidetes represent almost 90% of gut microbiota. Firmicutes phylum is composed of more than 200 different genera like Lactobacillus, Bacillus, Clostridium, Enterococcus e Ruminicoccus. Bacteroidetes phylum is represented by predominant genera like Bacteroides e Prevotella. Actinobacteria phylum is, in proportion, less abundant and mainly consisting of Bifidobacterium genus.
It is desirable that the “good” families are more numerous than the “bad” ones to benefit from and equilibrium status called “eubiosis”. When bad families grow excessively, a disequilibrium situation called “dysbiosis” is created.
The microbic ecosystem is denser in the distal region, the colon one.
The term “microbiome” refers to microbiota together with its environment.
Sometimes, “microbiome” is also used in the meaning of “collective genome” of microbiota.
Microbiota influences guest homeostasis (so, the equilibrium) performing several metabolic functions, not only digestive ones, thanks to its capability of producing and regulating a multitude of substances that reach systemic circulation and influence the activity of distal organs and of the whole organism.
Gut bacteria shape the intestinal barrier reinforcing it and they alert the immune system so that it doesn’t let potentially dangerous antigens, toxins or microbes enter the body, allowing just the entrance of necessary nutrients. Microbiota modulates inflammatory responses, so that nothing unwanted or disadvantageous enters the bloodstream.
- Organism’s digestive and metabolic processes participation
🡪 fermentation of dietary fiber and resistant starch undigestible for the host in the proximal part of large intestine
🡪 synthesis of vitamins like vitamin K and complex B vitamins
- Polyphenol extraction from ingested food
🡪 food polyphenols metabolism with production of more bioavailable secondary metabolites
- Gut barrier integrity maintenance
🡪 carbohydrates fermentation with short chain fatty acids (SCFA) production like butyrate and propionate, useful for growth, differentiation and metabolism in colonic enterocytes (cells that form the intestinal epitelium).
🡪intestinal epithelium tight junctions stabilization
🡪mucin synthesis stimulation
- Protection from colonization and invasion of potentially dangerous microorganisms
🡪synthesis of bacteriocins, molecules with antimicrobic activity
🡪production of lactic, propionic and acetic acids which reduce luminal pH, inhibiting the proliferation of pathogenic bacteria
🡪competition for nutrient substrates
🡪competition for epithelium adhesion
- Immune function modulation
🡪 influence on activity and immunity development at epithelial level, through the interaction with GALT (gut associated lymphoid tissue): induction of the proliferation of specific leukocyte sub-populations and citokyne synthesis stimulation (IL-2, IL-4, IL-10, 1L-12 and IFN-γ);
🡪influence on the activity and development of immunity at systemic level.
BRAIN-GUT AXIS and Leaky gut syndrome
The brain-gut axis is a bidirectional connection: the brain talks to the gut and the gut talks to the brain. A messy gut sends signals to the brain, just like a messy brain sends signals to the gut. Therefore, gastrointestinal discomfort can cause statuses of anxiety, stress or depression negatively influencing the emotional and cerebral area. About that, it is extremely important that intestinal membrane cells are very close to each other, creating the so called “tight junctions”. When this compactness among intestinal mucosa is lost, a condition of altered intestinal permeability is established, called “leaky gut syndrome”. The membrane lets bacteria, heavy metals, viruses, fungi and undigested molecules pass in the bloodstream: the first direct consequence is the instauration of an inflammatory state which leads to the onset of allergies, intolerances and autoimmune diseases. The most common symptoms associated to leaky gut syndrome can be: headache, tremors, irritability, depression, hyperactivity, joint and muscle pain, chronic fatigue, irritable bowel, constipation or diarrhea and, as already said, onset of allergies, food intolerances, thyroid changes and menstrual cramps.
Hippocrates himself was the first one to say, 2500 years ago, that everything originates from the gut, both for better or for worse.
So let’s take care of ourselves, modulate the dialogue between gut-second brain and first brain and, doing so, feed properly our bacterial friends, recognizing and appreciating their important role.
“Cibo, non Cibo e Microbiota Intestinale. La re-implantologia batterica”; edito da Società Italiana di Biologia Sperimentale. Sezione di Bologna “Oliviero Mario Olivo”; presidente: prof. Massimo Cocchi
• Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014 Aug;28(8):1221-38. doi: 10.1210/me.2014-1108. Epub 2014 Jun 3. PMID: 24892638; PMCID: PMC5414803.
• Rinninella E, Raoul P, Cintoni M, et al. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms. 2019;7(1):14. Published 2019 Jan 10. doi:10.3390/microorganisms7010014 •
• Katzung B.G. Basic and clinical pharmacology. Mc-Graw-Hill Education. 2015.
• Scarpellini E, Ianiro G, Attili F, Bassanelli C, De Santis A, Gasbarrini A. The human gut microbiota and virome: Potential therapeutic implications. Dig Liver Dis. 2015 Dec;47(12):1007-12. doi: 10.1016/j.dld.2015.07.008. Epub 2015 Jul 18. PMID: 26257129; PMCID: PMC7185617.
Morowitz MJ, Carlisle EM, Alverdy JC. Contributions of intestinal bacteria to nutrition and metabolism in the critically ill. Surg Clin North Am. 2011;91(4):771-viii. doi:10.1016/j.suc.2011.05.001
Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev. 1997 Mar;6 Suppl 1:S43-5. doi: 10.1097/00008469-199703001-00009. PMID: 9167138.
• Etxeberria U, Fernández-Quintela A, Milagro FI, Aguirre L, Martínez JA, Portillo MP. Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. J Agric Food Chem. 2013 Oct 9;61(40):9517-33. doi: 10.1021/jf402506c. Epub 2013 Sep 27. PMID: 24033291.
• Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, Szajewska H, Stahl B, Guarner F, Respondek F, Whelan K, Coxam V, Davicco MJ, Léotoing L, Wittrant Y, Delzenne NM, Cani PD, Neyrinck AM, Meheust A. Prebiotic effects: metabolic and health benefits. Br J Nutr. 2010 Aug;104 Suppl 2:S1-63. doi: 10.1017/S0007114510003363. PMID: 20920376.
• Ramakrishna BS. Role of the gut microbiota in human nutrition and metabolism. J Gastroenterol Hepatol. 2013 Dec;28 Suppl 4:9-17. doi: 10.1111/jgh.12294. PMID: 24251697.
• Plaza-Diaz J, Gomez-Llorente C, Fontana L, Gil A. Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics. World J Gastroenterol. 2014;20(42):15632-15649. doi:10.3748/wjg.v20.i42.15632
• “Sistema Immunitario” M. R. Di Fazio e P. Lagarde; 2021