Index IntroductionFunctions of the intestinal microbiotaDysbiosis and diseasesIntroductionRecent studies have allowed us to reach the conclusion that we are super organisms in which microbial symbionts perform essential physiological functions. The human microbiome has emerged as the crucial moderator in interactions between food and our bodies and can change our minds and health or play a critical role in a wide range of diseases. There are 52 bacterial phyla currently recognized on Earth, 5 to 7 of which reside in the gastrointestinal tract which is home to over 100 trillion bacteria. Firmicutes, Bacteroidetes and Actinobacteria are the 3 main phyla to which the majority of the gastrointestinal microbiota belongs. In my self-study essay I will talk about the importance of the gut microbiota and the role they play in the health of the host, as well as the potential links they have with certain diseases. We will first talk about the multiple functions performed by the microbiota in the immune and nervous systems, as well as their role in metabolism, homeostasis and protection against pathogen overgrowth. I will then go on to mention the potential link they may have with the following diseases: obesity, colorectal cancer, Clostridium difficile infection and inflammatory bowel disease. I will conclude with my personal opinion on the topic and on possible future perspectives and research to be carried out. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Functions of the Gut Microbiota The gut microbiota has an important role to play in immune, neuroendocrine, and metabolic interactions that stabilize and regulate their symbiotic relationship with the host. 1) Immunity and the nervous system: The gut barrier protects the internal environment of the host from the external environment and is made up of the epithelial and mucous layers. Disruption of its function increases intestinal permeability to commensal microbes and their products and leads to aberrant immune-inflammatory responses such as inflammation, allergy, and autoimmune disorders, controlled by dysregulated T cell response and molecular mimicry. The intestinal microbiota cross-regulates the physical and immunological functions of the intestinal barrier. Tight regulation of gastrointestinal T cell balance, such as the Treg/TH17 balance, is vital to maintain intestinal homeostasis and prevent an aberrant immune-inflammatory response. Recent studies have demonstrated that the gut microbiota has a role to play in regulating the host immune response and immunity at both local and systemic levels. Studies in germ-free mice have indicated that the gut microbiota facilitates the maturation of lymphocytopoiesis and hematopoiesis, as well as adaptive and innate immunity. The host microbiota and its SCFAs (short-chain fatty acids), also regulate the maturation and functionality of microglia, which are the tissue macrophages of the central nervous system (CNS) [8], also have an important role in maintaining homeostasis of microglia, which is crucial for maintaining the health of the central nervous system. The gut microbiota also has a modulatory role in the enteric nervous system (ENS), which communicates bidirectionally with the central nervous system to form the gut-brain axis by autonomously regulating the physiology and function of the gastrointestinal tract. The main component of the ENS is enteric glial cells (EGCs) which form the enteric glial network and regulate rods such as intestinal motility, immunoinflammatory reactions, blood flow andendocrine/exocrine. Various gastrointestinal disorders such as inflammatory bowel disease, infection-induced intestinal inflammation, neurodegenerative disorders, and motility disorders have all been linked to dysfunction of the ENS and EGC. Recent studies have shown that the close proximity of the gut microbiota and the ENS throughout the gastrointestinal tract allows them to modulate intestinal activity. function and development of the ENS. Studies in germ-free mice have shown a notable decrease in intestinal motility compared to specific pathogen-free mice and altered Schaedler flora counterparts and highlights the importance of the gut microbiota in the postnatal development of the ENS in the mid-distal gut. Finally, toll-like receptors (TLRs) play a fundamental role in maintaining intestinal homeostasis and the symbiotic relationship between the host and the intestinal microbiota. Expression of TLR4 likely gives the ENS the ability to react instantaneously to stimuli derived from the gut microbiota, which suggests that TLRs may be the link between the gut microbiota and the development of the ENS. All the points highlighted above highlight that the gut microbiota has a vast number of roles to play in the immune and nervous systems. 2) Metabolism: The gut microbiota facilitates host energy harvesting and metabolic efficiency through enrichment of amino acid, polysaccharide, micronutrient, and xenobiotic metabolism as revealed from human fecal samples using metagenomic sequencing techniques and 16S ribosomal RNA Fermentation of unabsorbed starch and soluble dietary fiber is another important role of the gut microbiota, with the end product in the form of SCFAs acting. as one of the energy substrates for the host and contribute an additional 10% of daily dietary energy for other metabolic processes. processes. SCFAs regulate energy homeostasis by stimulating GPR41-mediated leptin production. Studies in mice have shown a link between interactive host-microbe signaling and immuno-inflammatory crosstalk of the gut-brain axis as leptin exhibits pleiotropic effects on physiological functions such as appetite and energy metabolism along with immune response and sympathetic nerve activity. Gut microbes also synthesize vitamins which are micronutrients that show beneficial value for both microbial and host metabolism. Intestinal bacteria that produce vitamin K, (e.g. Bacteroides fragilis), anaerobically synthesize vitamin K2 which helps reduce the risk of cardiovascular disorders such as coronary heart disease by decreasing vascular calcification, lowering cholesterol levels and increasing HDL. The intestinal microbiota also exclusively synthesizes vitamins B5 and B12 which act as coenzymes for the production of cortisol and acetylcholine, vital for the correct functioning of the nervous system. Neuropsychological and hermatological disorders, as well as insomnia and gastrointestinal disorders have all been linked to vitamin B5 and B12 deficiencies. The gut microbiota also plays an important role in the co-metabolism of bile acids, which aid in digestion, cholesterol and lipid metabolism. In humans, 95% of bile acids are reabsorbed in the distal ileum. 5% of unabsorbed primary bile acids become secondary bile acids through bioconversion or deconjugation by acids of bile salts secreted by the colonic microbiota. They are subsequently partly reabsorbed in the colon and then transported back to the liver for conjugation. Unabsorbed secondary bile acids are excreted by the host. Primary bile acids esecondary ones are able to regulate bile acid production, glucose metabolism and perhaps even hepatic autophagy, by activating host FXR signaling. Secondary bile acids can also protect the host from a number of infectious pathogens and help shape the composition of the gut microbiota using antimicrobial properties that alter the integrity of the microbial cell membrane to cause leakage of intracellular contents and inhibit the growth of microbes intolerant to bile acids.3) Protection from pathobionts: the human microbiota protects the host from the excessive growth of pathogenic microbiota (pathobionts) using 2 mechanisms of action. Competition with pathogens for shared niches and nutrients and suppression of the pathogen by enhancing the host defense mechanism. Dominant members of the non-pathogenic gut microbiota occupy the niche and suppress pathogen growth and colonization. A decrease in dominant members of the microbiota during perturbation of the gut microbiome allows opportunistic pathogenic strains to colonize empty niches and lead to infection. Dysbiosis and diseases Dysbiosis is an imbalance in the taxonomic composition of the intestinal microbiota and can be caused by both external and host factors. External factors can include antibiotic use, diet and stress. Dysbiosis prevents the gut microbiota from maintaining the well-being of the host and can lead to an increase in pathogens leading to the unregulated production of microbially derived products or metabolites that can be harmful to the host and cause a variety of organ diseases local, systemic or remote. In short, dysbiosis is the possible link between the gut microbiome and disease manifestation. 1) Obesity: Obesity is a global health threat, affecting more than 600 million people worldwide. Obesity can be caused by a number of factors such as genetic, behavioral and environmental factors and is linked to the gut microbiome through its function in regulating host metabolism. High energy intake and decreased energy expenditure are classic signs of obesity and are linked to metabolic syndrome, causing excessive fat accumulation and leading to a greater risk of developing obesity-associated disorders, such as type 2 diabetes and mortality premature. The gut microbiota contributes to the development of obesity by facilitating increased digestion of food causing increased energy harvesting and increased fat deposition, suppressing lipoprotein lipase inhibitors to store triacylglycerides in adipocytes, and promoting hepatic DNL through expression of enzymes that synthesize hepatic fatty acids. Furthermore, increased endotoxic LPS from Gram-negative intestinal bacteria can lead to obesity-associated metabolic syndrome, obesity-associated insulin resistance, and low-grade inflammation. As seen in animal models, prebiotics or probiotics can be used through dietary intervention to selectively modulate microbial composition as a possible therapeutic approach to obesity-related metabolic disorder due to its association with gut microbiota dysbiosis. These are promising treatments for the future but more clinical. Studies and supporting data from human models are needed to demonstrate their success.2) Clostridium difficile infection (CDI): Clostridium difficile is a Gram-positive toxin and a spore-producing anaerobe and is a Firmicutes member in the gut microbiota. CDI is a serious disease with 453,000 cases resulting in death in America in 2011 alone.Diarrhoea, pseudomembranous colitis, sepsis and mortality in severe cases are some of the symptoms associated with CDI. Antibiotic administration can be a major risk factor for CDI, with 5 to 35% of people developing diarrhea as a side effect. CDI used multiple modes of horizontal gene transfer within strains and possibly commensal microbes in order to acquire resistance genes towards a range of antibiotics including clindamycin, erythromycin, chloramphenicol and linezolid. The exact mechanism of antibiotic-associated diarrhea remains unknown, but its correlation with CDI requires research into the link between C. difficile and the gut microbiome in a healthy state. The dominant gut microbiota is currently thought to protect the host from C. difficile overgrowth in the normal microbiome using colonization resistance mechanisms. While the researchers propose that primary bile acids serve as germinants for C. difficile spores and that secondary bile acids inhibit the vegetative growth of C. difficile. Antibiotic administration reduces secondary bile acid diversity by perturbing intestinal microbial communities. This makes the host more susceptible to CDI because there is a reduction in the bioconversion of primary bile acids to secondary antimicrobials and this leads to the growth of C. difficile. Increased amounts of vegetative C. difficile lead to diarrhea as toxin secretion damages the intestinal barrier and stimulates a severe inflammatory response and impairs ion absorption. Novel therapeutic treatments involving restoration of the gut microbiota have been developed through a better understanding of CDI and the role that antibiotic-induced microbiome dysbiosis must play in its pathogenesis. An example of this treatment is FMT, in which gut microbiota from healthy donor feces is used to restore gut homeostasis, and patients who received it showed a long-lasting increase in fecal microbial diversity and a high recovery rate of 90% compared to vancomycin by 60%. While studies showed that patients who received FMT had a 94% CDI cure rate with no disease recurrence observed in a 16-month follow-up. After receiving FMT patients showed signs of an increase in beneficial bacteria and increased plasma levels of the antimicrobial peptide LL-37 along with a reduction in proinflammatory cytokines. Studies using FMT indicate a strong association between the gut microbiome and the development of CDI. While more advanced studies are needed to uncover the exact beneficial strains and underlying mechanisms of FMT, this has great potential for the future and highlights the widespread use of microbiota-shifting therapy in combating CDI.4) Inflammatory Bowel Disease (IBD ): IBD is a group of idiopathic, multifactorial, persistent and recurrent gastrointestinal inflammations in two forms, CD and UC. In CD, inflammation can occur anywhere along the entire gastrointestinal tract while UC is limited to the large intestine. IBD affects 1.4 million people in Europe and 2.2 million in America and the common associated symptoms are abdominal pain, fever and recurrent diarrhoea. The disease pathogenesis mechanism for IBD is lacking, however we know that it combines environmental and host factors and there is a potential link between the gut microbiota and the development of IBD. Dysbiosis in the gastrointestinal microbiome may be a secondary consequence of gastrointestinal inflammation, through the development of antibodies against commensal microbial antigens and autoantigens leading to loss of microbiota.