The human microbiome. “The Forgotten Organ”. The Forgotten Organ. Within body of healthy adult, microbial cells are estimated to outnumber human cells ten to one (100 trillion microbial cells)
The human microbiome “The Forgotten Organ”
The Forgotten Organ • Within body of healthy adult, microbial cells are estimated to outnumber human cells ten to one (100 trillion microbial cells) • Vast majority of microbial species have not been analyzed, because their growth is dependent upon a specific microenvironment • Human Microbiome Project is studying these communities at different sites on the body, including nasal passages, mouth, skin, GI tract and UG tract ( http://commonfund.nih.gov/hmp/)
Interaction of human and our commensural community • We have evolved in the context of complex communities • Microbes play an important part of an organism’s phenotype, beyond just symbiosis • We cannot separate our genes from the context of our microbes
Human microbiome • Provide a wide range of metabolic functions that humans lack • Microbes include bacteria, eukaryotes and viruses • DNA based studies to identify and understand the functions of the community
Human Microbiome, cont’d • Gut microbiota of humans is dissimilar between individuals • Populations of different countries are similar, with the US having fewer species of gut microbes
Gut flora • Consists of microorganisms that live in the digestive tracts • Largest reservoir of human flora • Estimated to have a hundred times as many genes as there are in the human genome • 300 and 1000 different species of bacteria • Fungi and protozoa make up part
Escherichia coli, one of the many species of bacteria present in our gut
Gut flora, cont’d • Commensal (non-harmful) but also mutualistic relationship. • Microbes perform a host of useful functions such as • Fermenting unused energy • Training the immune system • Preventing growth of pathogenic bacteria • Regulating the development of the gut • Producing vitamins, such as biotin and Vit K • Producing hormones to direct the hose to store fats
Diet and Gut Flora • Gut micro flora mainly composed of 3 enterotypes, are necessary for the the digestion of carbohydrates, animal proteins, and fats. • They will vary, depending on diet, and as your diet changes, their percentages will change
Gut flora in human infants • GI tract of human fetus is sterile • During birth and shortly thereafter, bacteria from the mother and the environment colonize the infant’s gut. • Immediately after vaginal delivery, babies may have bacterial strains derived from the mothers’ feces • Vaginally born infants take up to one month for their intestinal microflora to be well established; caesarian section babies may take 6 months
Functions of gut bacteria • Have enzymes that human cells lack for breaking down carbs, turning them into SCFAs • SCFAs increase growth of gut epithelial cells, and may increase growth of lymph tissue • Rats raised in sterile environment have to eat 30% more calories to remain the same weight
More functions • Repress microbial growth through the barrier effect • Harmful yeasts and bacteria like Clostridium difficile are unable to grow excessively due to competition from the helpful gut flora • Process of fermentation lowers the pH in colon, preventing proliferation of bad bacteria
Functions regarding Immunity • Bacteria promote early development of gut’s mucosal immune system • Stimulate lymph tissue to produce antibodies to pathogens • Immune system recognizes and fights harmful bacteria, but leaves the helpful species alone
More immune functions… • Play a role in “toll-like receptors” molecules that help repair damage due to injury, like radiation • Allow gut ability to discriminate between pathogenic and helpful bacteria • Activate inflammatory cytokines • Create oral tolerance, which help IS be less sensitive to antigen once its been ingested.
Help to prevent allergies • Children who have allergies have more harmful species of of bacteria, and lower helpful species • Since helpful gut flora stimulate the IS and train it to respond properly to antigens, lack of these bacteria leads to an inadequately trained IS.
Prevent IBS • Some bacteria can prevent inflammation • Disease linked to good hygiene in children, lack of breast feeding, consumption of large amounts of sucrose and animal fat and use of antibiotics in early life. • Inversely linked with poor sanitation in early years of life and consumption of fruits, veggies, and unprocessed foods.
Effects of antibiotics • Can alter the numbers of gut bacteria, which can reduce ability to digest • Can cause diarrhea by irritating the bowel directly, changing the levels of gut flora, and allowing pathogenic bacteria to grow • Creates antibiotic resistant bacteria in gut • Probiotics rely on a few strains of good bacteria;
Role in disease • Bacteria in digestive tract have pathogenic and health promoting roles • Can produce toxins and carcinogens • Bacteria have been related to sepsis and colon cancer, IBD, Crohn’s, Ulcerative Colitis • Balance is critical: harmful if numbers are too high or too low
Gut bacteria may affect arteries • Different mixes of gut microbes help determine whether people will have heart attacks or strokes brought on by plaque • HT disease patients carry fewer microbes that make anti-inflammatory and anti-oxidant compounds and more inflammation-producing bacteria (Dec 4 Nature Communications/Science News 1/12/2013,p 24))
Obesity • Obese mice lacking leptin have distinct gut flora population • Microbe colonies are different between obese and lean humans • Different species of flora have different energy reabsorbing potential…could lead to an increase in weight despite decrease in food
Role in disease, cont’d • Some bacteria are associated with tumor growth and others prevent tumors • Helpful bacteria can be harmful if they get outside of intestinal tract • Increased gut lining permeability can occur in “leaky gut syndrome”, or cirrhosis
Leaky Gut Syndrome • Means increased intestinal wall permeability • Just now being investigated; not recognized as a diagnosis • Hypothesized to be caused by increased permeability of the gut wall resulting from toxins, poor diet, parasites, infection or medications • Leaky gut allows toxins, microbes, indigested food, waste to leak through gut • Could cause immune reactions (rheumatoid arthritis, lupus, asthma, Type I diabeties, etc.)
T helper 17 cells • Recently discovered to play role in inflammatory process • Important anti-microbial barrier • Excessive amounts hypothesized to play role in autoimmune diseases such as MS, psoriasis, Type I diabetes, rheumatoid arthritis, Crohn’s • Autism spectrum disorders being investigated • Specific bacteria direct their differentiation in the mucosa of the gut
How does body differentiate good and bad • SI function of sorter, teaching IS to separate self from non-self • Oral tolerance:gut flora train innate IS to recognize self • If not “self” IL-12 in Peyer’s Patches inducing inflammation
Appendix • Immune tissue and antibodies are concentrated • Houses large numbers of bacteria in biofilms that offer services to our gut • Serves as an incubator, allowing for regeneration • When severe illness wipes out good bacteria, appendix can regenerate
Appendix, cont;d • Appendix in developed countries is infrequently challenged by pathogens and appendicitis is more common • In developing countries, humans get very sick from intestinal parasites • Perhaps appendix, through its role of replenishing the gut, is being kept healthy
Because nearly 70% of the immune system is localized to the digestive tract, a state of controlled physiologic inflammation,along with environmental contact with commensal bacteria, is essential for proper development of the immune system.
Fecal Transplants • Transplanting fecal matter directly into gut of someone suffering from a number of intestinal illnesses, including various inflammatory diseases, C Diff overpopulation, etc,has shown great promise • Still in experimental stage.
Bacteriophage • A virus that infects and replicates within bacteria, killing them. • Phages are all over - in soil, sea water, intestines, etc. • Use for over 90 years in the Eastern Europe against bacterial infections • Possible therapy against multi-drug resistant strains of bacteria.
Resources • “Integrative Gastroenterology”, by Gerard E. Mullin • “The Wild Life of our Bodies: Predators, Parasites, and Partners That Shape Who We Are Today”, by Rob Dunn • Ted.com “Meet Your Microbes” Jonathan Eisen, 2012”