Normal commensal flora: applied importance

#normal microbiota#importance

1. NORMAL COMMENSAL FLORA AND THEIR APPLIED IMPORTAN CE Presented by: Dr. Devyashree Medhi Post Graduate Trainee (Third Year) Dept. of Microbiology Gauhati Medical College and Hospital Moderator: Dr. Lahari Saikia Professor and Head Dept. of Microbiology Gauhati Medical College and Hospital

2. CONTENTS INTRODUCTION SITES AND DISTRIBUTION INTRODUCTION OF NORMAL FLORA INTO HUMAN BODY FACTORS THAT CONTRIBUTE TO BACTERIAL GUT COMMPOSITION APPLIED IMPORTANCE OF NORMAL MICROBIAL FLORA MICROBIOTA IN DISEASE

3. INTRODUCTION Normal flora or resident microbiota is the diverse group of microbial population that every human harbors on every surface of the body exposed to the external environment. Bacterial cells outnumber human cells by 10:1 ratio. They typically fall into one of the following two categories: Resident flora: They are permanent members of the community and when disturbed they again re-establish themselves. They are beneficial to the host. Transient flora: They colonize for a short duration and most of them are potential pathogens.

4. Most of the normal flora consist of bacteria and to a lesser extent fungi Overall, anaerobic flora predominates over aerobes The presence of viruses and parasites are doubtful. Although life is possible without normal residential flora, they are indispensable in maintaining the health and normal function of the host.

5. SITES Skin Conjunctiva External ear Nose, nasopharynx and sinuses Oral cavity Upper respiratory tract Gastrointestinal tract Genitourinary tract

6. Distribution of the human microbiome in the most representative body sites Vaginal Bacteroides Mobiluncus Group B streptococci Peptostreptococci CONS

7. INTRODUCTION OF NORMAL FLORA INTO THE HUMAN BODY

8. . The presence of the normal microbial flora in a given anatomical site depend on the following factors: Local temperature Moisture pH Presence of certain nutrients and inhibitory substances Environment (hospital/community) Immune status of the individual The gut composition of infants and toddlers varies significantly with time. Flora resembling that of adults is achieved by approximately 3 years of age.

9. FACTORS THAT CONTRIBUTE TO BACTERIAL GUT COMPOSITION

10. APPLIED IMPORTANCE

11. Normal flora is indispensable in maintaining proper nutritional status in the host They synthesize and excrete vitamins in excess of their own needs, which can be absorbed as nutrients by their host. They extract additional calories from otherwise indigestible oligosaccharides. They aid in the proper utilization of nutrients by modulation of absorptive capacity of the intestinal epithelium.

12. In humans, enteric bacteria secrete Vitamin K and Vitamin B12 and certain other vitamins of the B-complex group. Gut Bifidobacterium strains conjugate dietary linoleic acid also known as Vitamin F. It has a wide variety of biological effects like formation of lipids in the cell membrane, prostaglandins, leukotrienes e.t.c . Oral microbiota is required for reduction of dietary nitrate to biologically active nitrite which, among other functions, is essential for protecting the cardiovascular system and the gastric mucosa.

13. Prevent colonization by pathogen Normal microbiota provides its host with a physical barrier to incoming pathogens by competitive exclusion, such as occupation of attachment sites, consumption of nutrient sources, maintaining an acidic environment and production of antimicrobial substances. They also stimulates the host to produce various antimicrobial compounds the secretion of which is enhanced in acidic conditions. This has been demonstrated that germ-free animals can be infected by 10  Salmonella  bacilli, while the infectious dose for conventional animals is near 10 6  cells.

14. Stimulate the development of certain tissue Bacterial colonization of the intestine plays a major role in the post-natal development and maturation of the immune and endocrine systems and, therefore, the central nervous system. Experimental data suggest a role of enteric bacteria in the gut–brain axis. There is a substantial body of evidence to link the pathogenesis of irritable bowel syndrome with gut bacteria dysbiosis. The symptoms of autism typically become apparent before a child is 3 years old. Some evidence supports the alterations of the fecal microbiota in patients with autism, with an increase in several subtypes of Clostridium. In some cases, treatment with non-absorbed antibiotics can improve symptoms.

15. Development of host’s defense mechanisms The importance of the gut microbiota in the development of both the intestinal mucosal and systemic immune systems can be readily appreciated from studies of germ free animals. Germ free animals contain abnormal numbers of several immune cell types and immune cell products. They have deficits in local and systemic lymphoid structures. Spleens and lymph nodes are poorly formed. Peyer’s patches are hypoplastic and the number of mature isolated lymphoid follicles are decreased. The number of their IgA-producing plasma cells is reduced, as are the levels of secreted immunoglobulins. They also exhibit irregularities in cytokine levels.

16. Probiotics Probiotics are live micro-organisms which, when administered in adequate amounts as part of food, confer a health benefit on the host. Probiotics may play a beneficial role in several medical conditions, including antibiotic induced diarrhea, gastroenteritis, irritable bowel syndrome, inflammatory bowel disease, cancer, depressed immune function, infant allergies, failure-to-thrive, hyperlipidemia, hepatic diseases, Helicobacter pylori infections, and others, all of which were suggested by certain research studies to improve with the use of probiotics

17. Probiotic microbes exert beneficial effect via a wide array of actions. These include resistance to colonization production of antimicrobial substances inhibition of pathogen adhesion degradation of toxins stimulation of local and peripheral immunity stimulation of brush border enzyme activity stimulation of secretory-IgA prevention of microbial translocation. 

18. The major source of cholesterol in the human body includes biosynthesis by the liver and absorption by the intestines. These two factors determine the overall cholesterol level. The hypo- cholesterolemic effect of the probiotics has also been attributed to their ability to bind cholesterol in the small intestines. Recent research has found that several pathways may be involved, but these mechanisms are still not clearly understood. The overall cholesterol reduction mechanism of probiotic microorganisms are represented in Figure.

19. Prebiotics Prebiotics are nondigestible dietary ingredient that beneficially affects the host by selectively stimulating the growth or activity of a limited number of bacteria in the colon.  They are not digestible by human enzymes. Rather, they are fermented and digested by the microbiota of the intestine. Fructooligosaccharides , inulin, oligofructose, lactulose, and galactooligosaccharides have been identified as prebiotics. The combination of probiotics and prebiotics is termed ‘ synbiotic ’, and is an exciting concept aimed at optimizing the impact of probiotics on the gut microbial ecosystem.

20. Fecal microbiota transplantation Fecal microbiota transplantation is the administration of of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient’s gut microbial composition and confer health benefits. FMT has been used to successfully treat recurrent  Clostridium difficile  infection. There are preliminary indications to suggest that it may also carry therapeutic potential for other conditions such as inflammatory bowel disease, obesity, metabolic syndrome, and functional gastrointestinal disorders. The major concern about this approach is the potential risk of transmission of infectious diseases.

21. Preventative and therapeutic purposes Oxalobacter formigenes has the ability to degrade dietary oxalates, reducing urinary oxalate excretion, which prompted its successful use in clinical trials as a therapeutic and prophylactic option in calcium oxalate nephrolithiasis and associated renal failure. Furthermore, gut inhabitants can prove invaluable in preventing adverse outcomes following inadvertent environmental exposure to toxic compounds: the toxicity of hydrazine, a highly toxic compound used in a variety of industrial processes, is greatly reduced by the gut microbiota.

22. Dietary modifications for preventative and therapeutic purposes It has been observed that phenolic compounds have the ability to reduce or reverse the development of colitogenic changes at the intestinal mucosa, thus offering a prophylactic and sometimes a therapeutic means against colorectal carcinomas. The individual’s microbiota composition and its ability to bio-transform nutritional compounds with potential medicinal significance should be considered when recommending dietary interventions.

23. MICROBIOTA IN DISEASE Mechanisms of fine balance

24. Antibiotic-associated diarrhea Antibiotic-associated diarrhea is caused by an altered balance in gut microbial communities, resulting in both decreased fermentation of indigestible carbohydrates and rapid overgrowth of opportunistic micro-organisms with potential pathogenicity. It ranges from mild episodes that resolve when antibiotics are stopped to serious complications such as toxic megacolon, bowel perforation and death. Risk is increased with different clinical conditions such as extremes of age, co-morbidity, oral broad spectrum antibiotics, prolonged antibiotic duration, previous episodes of antibiotic-associated diarrhea and hospitalization.

25. Autoimmunity and related disorders A number of studies using molecular techniques confirm that the gut microbial ecosystem differs between children with and without atopic eczema. In fact, children born by means of caesarean section are colonized by bacteria originating from the hospital environment and not from maternal skin. A cohort study by Penders et al. suggests that early colonization by Escherichia coli increases the risk of developing eczema and colonization with Clostridium difficile is associated with a higher risk of eczema, recurrent wheeze and allergic sensitization. Undoubtedly, there are other environmental conditions, such as feeding regimen, antibiotic intake or hygiene, which are well-recognized risk factors

26. Pseudomonas aeruginosa  Pseudomonas aeruginosa is an example of a mutualistic bacterium that can turn into a pathogen and cause disease if it gains entry into the circulatory system. It can result in infections in skin, bone, joint, gastrointestinal, and respiratory systems. However, it produces antimicrobial substances such as pseudomonic acid that is exploited commercially as Mupirocin. This works against staphylococcal and streptococcal infections. Pseudomonas aeruginosa also produces substances that inhibit the growth of fungus species such as  Candida krusei ,  Candida albicans ,  Torulopsis glabrata ,  Saccharomyces cerevisiae  and  Aspergillus fumigatus . It can also inhibit the growth of  Helicobacter pylori.

27. Bacterial translocation Intestinal bacteria play a role in the pathogenesis of sepsis by bacterial translocation, defined as the passage of viable bacteria from the gastrointestinal tract through the epithelial mucosa. Extensive work on bacterial translocation has been performed in animal models and occurs notably in hemorrhagic shock, burn injury, trauma, intestinal ischemia, intestinal obstruction, severe pancreatitis, acute liver failure and cirrhosis.

28. Metabolic syndrome In animal models, it seems that transplantation of gut microbiota from obese mice to non-obese, germ-free mice resulted in transfer of metabolic syndrome-associated features from the donor to the recipient. The mechanisms advocated are the provision of additional energy by the conversion of dietary fibre to SCFA, effects on gut-hormone production and increased intestinal permeability, causing elevated systemic levels of lipopolysaccharides. The contact with these antigens seems to contribute to low-grade inflammation, a characteristic trait of obesity and metabolic syndrome. Presumably, obesity affects the diversity of the gut microbiota and, probably, the way individuals harvest energy from nutrients. However diet or other undetermined variables may also account for the observed microbiome changes. Further research on human subjects must be conducted.

29. Gut microbiota and cancer therapy The relationship between gut resident microbiota and their host is complex. Some bacterial subpopulations are able to rise during gut dysbiosis and, in turn, to trigger the formation of an inflammatory and pro-cancerogenic environment. On the other hand, many gut derived probiotics like lactobacillus rhamnosus are able to protect the host, re-establishing the conditions of a healthy intestinal microbiota within dysbiotic patients, including cancer patients.

30. Three parallel studies identified specific gut species populating the gastro-intestinal tract of cancer immunotherapy responders, are able to improve the efficacy of immunotherapy treatments. That questions the usage of both probiotics and FMT in cancer therapy, either as tools to repopulate cancer patients’ damaged intestine or even as proper adjuvants in immunotherapy and other kinds of anti-cancer therapies. Correspondingly, care needs to be pursued as patients are often immunocompromised, therefore it is important to evaluate the specific side effects of administering selected bacterial species to such sensitive individuals. 

31. Reference Linking the gut microbiota to human health. Alonso VR, Guarner . British Journal of Nutrition (2013), 109, S21–S26 doi:10.1017/S0007114512005235 Review Article Effects of Probiotics, Prebiotics, and Synbiotics on Hypercholesterolemia: A Review. Anandharaj M, Shivashankari B, Rani RP. Chinese Journal of Biology .Volume 2014, Article ID 572754. http://dx.doi.org/10.1155/2014/572754 Gupta S, Allen- Vercoe E, Petrof EO. Fecal microbiota transplantation: in perspective.  Therap Adv Gastroenterol . 2016;9(2):229–239. doi:10.1177/1756283X15607414 Ma L, Hu L, Feng X, Wang S. Nitrate and Nitrite in Health and Disease.  Aging Dis . 2018 Oct 1;9(5):938-945. doi : 10.14336/AD.2017.1207. PMID: 30271668; PMCID: PMC6147587. Gut Microbiota in Health and Disease.Sekirov I, Russell SL SHANNON L, Antunes LCM, Finlay BB. Physiol Rev 90: 859–904, 2010; doi:10.1152/physrev.00045.2009. Gut microbiota and cancer: From pathogenesis to therapy. Vivarelli S, Salemi R et al. Cancers (Basel).2019 jan;11(1) 38.