WORLD DIGESTIVE HEALTH DAY 29th May. Bangladesh Gastroenterology Society creating awareness nation-wide.

Importance in health and disease Slogan Gut microbes- Importance in health and disease

GUT FLORA AND HEALTH Dr. Jimma Hossain MBBS, MD (Gastro) Assistant Professor Department of Gastroenterology Rangpur Medical College & Hospital

Gut flora Gut flora consists of a complex of microorganism species. Human intestine carries about 100 trillion microorganisms. Ten times greater than total cell in body.

Gut flora About 500 different species live in gut. Bacteria makeup the majority. Over 99% of bacteria are anaerobes. Fungi, protozoa and archaea also part of gut flora,but little is known about their activities.

Gut flora Most bacteria belong to genera Bacteroids,Clostridium,Fusobacterium,Eubacterium,Ruminococcus,Peptococcus,Peptostreptococcus and Bifidobacterium. Bacteroids alone constitute 30%. Fungi include Candida, Saccharomyces, Aspergillus and Penicillium. Archea another large class of flora important for metabolism of bacterial products of fermentation.

Gut flora and diet Association between concentration of microbial community and dietary components. Prevotella with carbohydrate based diet. Bacteroids with animal protein diet. Gut flora can be changed by following a long term diet.

Acquisition of gut flora At birth digestive tract is sterile. Colonised by microbes within first few days. All infants initially colonized by E.coli and Streptococci and subsequently anaerobes predominate. Breast fed babies predominated by Bifidobacteria. With introducton of other foods,a diverse microbial population develops.

Gut flora and health Research suggests relationship between gut flora and humans not merely commensal ,but rather mutualistic. Though people can survive without gut flora,microorganisms perform a host of useful functions.

Gut Flora A healthy digestive system should contain at least 80-85% friendly bacteria to prevent diseases caused by organisms like E. coli & salmonella. Stomach 10¹-10³ cfu/ml Duodenum 10¹-10³ cfu/ml Jejunum/Ileum 104-107 cfu/ml Colon 10¹¹-10¹² cfu/ml

Useful Functions Recycle energy by fermenting unused energy substrate. Early development & training of the immune system. Prevention of the growth of harmful pathogenic bacteria. Regulation of the development of gut. Production of vitamins such as biotin, folate and vitamin K.

Useful Functions Antidiabetic,anticarcinogenic,hypocholesterolemic role. However,in certain conditions,some species capable of causing disease by producing infection,increasing cancer risk for the host.

Fermentation Saccharolytic - more favorable. Proteolytic- less favorable.

Saccharolytic fermentation Carbohydrates fermented into short chain fatty acids(SCFAs). Acetic acid,propionic acid and butyric acid. These are used by enterocytes and other cells and helps mineral absorption. Butyric acid provides energy to gut cells and prevents cancer.

Potential Mechanisms of Anti-neoplastic Action Angiogenesis Inflammation Immunosurveillance Proliferation Apoptosis Butyrate

Proteolytic Fermentation Breaks down proteins like enzymes,dead host and bacterial cells,collagen,elastin. Can produce toxins and carcinogens in addition to SCFAs.

Trophic effects SCFAs increase growth of intestinal epithelial cells and control proliferation and differentiation. Growth of the lymphoid tissue near the gut. Prevents cells from injury. Prevents cancer.

Suppression of pathogenic microbial growth Prevents harmful bacteria through competitive exclusion. By competing for nutrition and attachment sites to epithelium. Produce bacteriocins that kills harmful microbes. By producing acids during fermentation lowers colonic PH and thus prevents proliferation of harmful species and facilitating helpful species. By influencing mucosal barrier. By influencing immune function.

Immunity Gut flora have regulatory effects on mucosal immune response. Key in promoting early development of gut’s mucosal immune system. Stimulate lymphoid tissue associated with the gut to produce antibodies to pathogens.

Modulation of immune response by flora Immunity Modulation of immune response by flora Stimulation of mucosal immunity * Better oral vaccine responses * Control infections Suppression of mucosal immunity * Reduce allergy * Reduce inflammation

Prevention of allergy Can influence tolerance of gut immune system to antigens Helpful gut flora stimulate immune system and train it to respond properly to antigens. Lack of these bacteria in early life leads to an inadequately trained immune system that over reacts to antigens.

Prevention of allergy Composition of gut flora varies in patients with/without allergies. In allergy: Bacteroides, Bifidobacteria S.aureus, C.difficile

Prevention of inflammatory bowel disease SCFAs prevent IBD. Some form of bacteria can prevent inflammation. Linked to good hygiene in youth. Inversely linked with poor sanitation during first year of life. Antibiotics that kill native bacteria. High concentration probiotics decrease inflammation.

Alteration in flora balance Inflammation Antibiotic use AAD Irritating bowel directly Changing levels of gut flora, alteration in flora balance. Allowing pathogenic bacteria to grow Decreased ability to ferment CHO and bile acids Over growth of C.difficile Gut flora composition also changes in severe illness, ischaemia, immune compromise.

Alteration in flora balance Pharmabiotics Generic term to encompass any form of therapeutic exploitation of commensal flora Use of live probiotic bacteria,pre-biotics,synbiotics(genetically modified commensal). Pre-biotics : dietary components that foster the growth of micro organisms in the gut Pregnancy. Wt loss.

Role in disease Have pathogenic properties in addition to their health-inducing ones. They can produce toxins and carcinogens.

Role in disease Implicated in conditions as MOF,sepsis,colon cancer and IBD. A major factor in health is the balance of bacterial numbers ; if too high or low,will harm the host.

Role in disease Some genera-Bacteroids and Clostridium associated with in increase in tumor growth rate. Lactobacillus and Bifidobacteria are known to prevent tumor formation.

Role in disease Bacterial translocation in certain conditions causes sepsis. Implicated in colitis, obesity.

Conclusion The gastrointestinal tract is now considered one of the most complex microbial ecosystem on earth. Till to date, little is known about this ecosystem. Researches are going on to explore undiscovered aspects of gut flora in health & disease.