Gut Microbiota and Disorders PDF

24.8 Disorders Attributed to the Gut Microbiota Inflammatory Bowel Disease (IBD) – Chronic inflammation of the gut and disruption of homeostasis (dysbiosis). – Antibiotic use increases the risk of developing IBD. – Once developed, IBD may be transmissible between family members. –...

24.8 Disorders Attributed to the Gut Microbiota Inflammatory Bowel Disease (IBD) – Chronic inflammation of the gut and disruption of homeostasis (dysbiosis). – Antibiotic use increases the risk of developing IBD. – Once developed, IBD may be transmissible between family members. – Individuals with IBD have lower gut microbiome diversity. (Figure 24.18) Metagenomic analysis of human gut microbiota in healthy subjects and patients with inflammatory bowel disease (IBD) revealed a tendency toward fewer nonredundant bacterial genes, thus fewer bacterial species, in patients with IBD. Figure 24.18 The Role of the Gut Microbiota in Obesity One of the main activities of the intestinal microbiota is to break down and ferment dietary fibers into volatile fatty acids (VFAs), including acetate, propionate, and butyrate. The host absorbs these acids, and humans obtain about 10% of their daily energy requirements from them.  The Role of the Gut Microbiota in Obesity: An experimental Mouse Model – Normal mice have 40 percent more fat than germ-free mice with the same diet. When germ-free mice were given normal mouse microbiota, they started gaining weight. – Mice that are genetically obese have different microbiota than normal mice. Obese mice have more Firmicutes. (Figure 24.19) The Gut Microbiota and Human Obesity – The transferability of gut microbiota might be possible but complex: genetics, diet, method of transplantation, microbe adaptation, etc. (Figure 24. 20) IV. Modulation of the Human Microbiome 24.10 Antibiotics and the Human Microbiome 24.11 Probiotics and Prebiotics Antibiotics and the Human Microbiome Oral antibiotics decrease ALL microbes in the human gut (both target and non-target). Use of antibiotics during the first few months of life increases the risk of developing IBD and other disorders related to dysbiosis (microbial imbalance or maladaptation). Clostridium difficile infections are associated with antibiotic use. – Clostridium difficile is a spore-former and generally antibiotic resistant. – An experimenting therapy for Clostridium difficile infection is a fecal transplant. (Figure 24.23)  Clostridium difficile “difficile” is the Latin for “difficult” (to get rid of and to treat). Strict anaerobic metabolism and gram-positive cell Producing two toxins: an enterotoxin (toxin A) that attracts neutrophils and stimulates their release of cytokines, and a cytotoxin (toxin B) that increases permeability of the intestinal wall and subsequent diarrhea. Spore formation allows the organism to persist in the hospital environment and resist decontamination efforts. Clostridium difficile www.medscape.com http://ibdpatient2patient.com/2015/02/05/treating-c-diff-now-in-the-future/  C. difficile disease C. difficile is resistance to antibiotics such Antibiotic-associated as clindamycin, cephalosporins, and colitis: gross section of fluoroquinolones so that allows C. difficile the lumen of the colon. to overgrow the normal intestinal Note the white plaques of fibrin, mucus, and bacteria in patients exposed to these inflammatory cells antibiotics and produce disease. overlying the normal Causing antibiotic- red intestinal mucosa. associated gastrointestinal diseases: ranging from a relatively benign, self-limited diarrhea to severe, life- threatening pseudomembranous colitis. http://ibdpatient2patient.com/2015/ 02/05/treating-c-diff-now-in-the- future/  Fecal Microbiota Transplantation (FMT) The screening of donor health in FMT is stringent: those with transmittable diseases, metabolic syndromes and other chronic diseases are excluded. People who have frequent travels are also ineligible. Testing to treat recurrent C. difficile infection and the applicability of FMT in other diseases such as obesity, irritable bowel syndrome and ulcerative colitis etc. Donor identification Infection screening Stool collection Infusion Colle cte d stool is d ilute d with ste rile sa line a nd The superna ta nt is infused into filte re d , a nd the re ma ining solution re se mble s pa tients—either to the sma ll intestine te a or to the colon using a n endoscope http://www.iso.cuhk.edu.hk/english/publications/CUHKUPDates/article.aspx?articleid=1658 Association with antibiotic use and treatment After a fecal transplant Figure 24.23  of recording Exam - see last pat of Microbiome therapeutics SER-109 is an investigational, oral, biologically-derived microbiome therapeutic designed to prevent recurrence of C. difficile in adults. SER-109 is a consortium of purified bacterial spores of multiple Firmicute species, manufactured by fractionating targeted bacteria from stool of healthy human donors with further steps to inactivate and remove potential pathogens. The FDA has granted SER-109 Breakthrough Therapy designation and Orphan Drug designation. In a Phase 3 clinical trial, SER-109 led to a highly statistically significant reduction in C. difficile recurrence compared to placebo, with a favorable safety profile https://ir.serestherapeutics.com/