Beyond the Scope: The Microbiome & The Future of Gastroenterology Robynne Chutkan, MD, FASGE Digestive Center for Wellness, LLC MedStar Georgetown University Hospital
Rapid Identification of Microbes
Human Microbiome Project Gut microbiome is highly personalized Lots of variation in vaginal organisms Mouth and skin microbes less personalized 1. Many microbial genes not yet sequenced 2. Known factors can t explain variations 3. Tremendously complex communities Nature 2017
The Gut Microbiome Digest food Produce SCFA Synthesize vitamins Metabolize drugs Neutralize toxins Maintain gut lining Train immune system Turn genes on and off
Differences in Birth Method C-section Vaginal Allergies Asthma Autoimmune diseases Obesity
The Developing Microbiome
5 Days of Antibiotics
Proton Pump Inhibitors Affect the Gut Microbiome 2000 patients (PPI users vs. non-users) PPIs - significant decrease in diversity PPIs - changes in 20% of bacterial taxa increase in Enterococcus, Streptococcus, Staphylococcus and Escherichia coli. Less healthy gut microbiome in PPI users Predisposes to C. difficile infection Predisposes to enteric infections Gut 2015
Effects of PPIs more prominent than effects of antibiotics!
Autoimmune Diseases
HYGIENE Hypothesis
Multiple Sclerosis
Helminths Infestation
Inflammatory Bowel Diseases Dysregulation of mucosal immune system Inappropriate response to commensal microbes
Genetic Basis for IBD > 100 host susceptibility loci Familial clustering Racial and ethnic differences Family history in 10-20% 10-fold increased risk in relatives
Antibiotics Associated with Increased Risk of New-Onset Crohn's Disease Meta-analysis 7,208 IBD patients Pooled odds ratio 1.57 Risk of CD in children most markedly increased All antibiotics except PCN strongly associated Metronidazole or fluoroquinolones highest risk American Journal of Gastroenterology 2014
Rural Residence During Early Life is Associated with a Lower Risk of IBD Association strongest in: Young children and adolescents Small family size Early exposure to antibiotics Association lowest in: Children exposed to rurality in 1 st 5 years Early life exposure to farm animals American J of Gastroenterology 2017
Microbial Signature in Crohn s Increase in mucosally associated bacteria Decrease in microbial diversity Decreased production of butyrate Enterobacteriaceae Adherent/invasive E. coli Clostridial group Protective faecalibacterium Roseburia Firmicutes
Irritable Bowel Syndrome Most common visceral pain syndrome Abdominal pain + change in bowel habits
Does Dysbiosis Cause IBS? Gut microbial differences in healthy vs. IBS Findings in rodent models Effect of antibiotics Post-infectious IBS Response to FODMAP diet Interactions between gut microbiota & the brain Increased Firmicutes to Bacteroidetes ratio
IBS Subtype Defined by Specific Alterations in Fecal Microbiota Microbiome sequencing: 37 IBS patients (diarrhea/constipation/alternators) 20 age and gender-matched controls Microbial signatures for: Colonic transit, depression Microbiota-specific subgroups: High Firmicutes Low Bacteroidetes BMJ 2011
Bifidobacterium-Rich Donor Positive Predictor for Successful FMT in IBS Single-arm, open label study, Rome III criteria 10 patients, FMT via colonoscopy End points: improvement in Bristol stool scale change in intestinal microbiota psychological status Clinical response in 6/10 patients at 4 weeks Greater increase in diversity in responders Greater abundance of Bifido in effective donors Digestion 2017
Celiac Disease 1 in 4 of European ancestry carry genes Genes necessary but not sufficient Immune system trigger New onset celiac disease strongly associated with antibiotic use People with celiac disease 40% more likely to have received antibiotics shortly before diagnosis
Antibiotic Exposure and the Development of Celiac Disease Swedish Prescribed Drug Register Histopathology from 2,933 people with celiac Antibiotics and celiac: 1.4 OR (95%) INTESTINAL DYSBIOSIS MAY PLAY A ROLE IN THE PATHOGENESIS OF CELIAC DISEASE BMC Gastroenterology 2013
A Tale of Two Cities
Impact of Diet in Shaping Gut Microbiota Comparative study Italy versus Burkina Faso European children consuming a Western diet: greater abundance of gram-positive bacteria (Firmicutes) African children - high fiber, vegetarian diet: greater abundance of Bacteroidetes higher microbial richness more species diversity lower prevalence of pathogenic strains high levels of SCFA PNAS 2010
Diet & the Gut Healthy bacterial populations living in the gut may not just exclude disease-causing bugs; by pumping out beneficial compounds, they may actively help to suppress disease
Diet Swap has Dramatic Effects on Colon Cancer Risk for Americans and Africans" 20 African Americans & 20 Africans (rural SA) Swapped diets for two weeks American group on African diet less inflammation in the colon reduced biomarkers of cancer risk African group on American diet dramatic increase in cancer risk after two weeks Imperial College, London 2015
MACs
Faecalibacterium prausnitzii Protective role in metabolic diseases Strong correlation with SCFA production More prevalent in vegans (inulin) Associated with reduced risk for cardiovascular disease, colon cancer, diabetes and obesity
Diet Rapidly & Reproducibly Alters Human Gut Microbiome Nature, January 2014
Biodiversity in the Human Gut Greater microbial diversity is associated with better ability to deal with stressors like opportunistic pathogens or dietary perturbations. Individuals with a disease are more likely to have alterations in gut microbial communities. Mayo Clinic Proceedings 2014
Gut Microbial Imbalance Nature Reviews Immunology Vol 9, May 2009 313
Effect of a Low-Complex Carbohydrate Diet on IBD A retrospective review to assess the effectiveness of the Specific Carbohydrate Diet (SCD) in improving quality of life and reducing frequency and severity of flare ups in patients with Inflammatory Bowel Disease Chutkan, et al. DDW 2014
Patient Characteristics Age range 16-69 (mean = 39.25) Gender Diagnosis Average number of years of disease Past surgery 9 female / 3 male 3 UC / 9 CD 2-23 (mean = 10) 5 out of 12 patients
Average Time on Diet in Days Average Time on Diet 2500 2000 1500 1000 Time on Diet (in days) 500 0 1 2 3 4 5 6 7 8 9 10 11 12 Patient
Time on Diet (in Days) Time on Diet Before Improvement 140 120 100 80 60 Average Time (in Days) 40 20 0 1 2 3 4 5 6 7 8 9 10 11 12 Patient
Medication Mean time on diet before improvement Number of patients able to stop or decrease medication(s) Number of patients able to stop medication(s) Number of patients able to decrease medication(s) 38 days 7 out of 12 (58%) 5 out of 12 (42%) 2/12 (17%)
Endoscopic Results Colonoscopy in 8 patients 6 out of 8 showed mucosal healing
Conclusions Nutritional therapy is a viable therapeutic option for management of IBD Can result in improvement of symptoms, mucosal healing, and a reduction or discontinuation of medication DIRECT CORRELATION BETWEEN IMPROVEMENT AND THE AMOUNT OF FIBROUS PLANTS CONSUMED
Veleo diet Lots of high-fiber plant matter in the form of fresh vegetables and fruits Microbe-boosting whole grains and legumes that contain food for our microbes to eat The option of a small amount of protein and fat from animal sources
Green light foods Fruits Vegetables Nuts Nut butters Seeds Legumes Squash, sweet potatoes Olive oil Coconut oil Buckwheat Amaranth Millet Quinoa Organic raw honey Brown, red, & black rice Oats
Emphasize these foods Fermented foods Onions Leeks Leafy greens Cruciferous veggies Garlic Asparagus (include stems) Broccoli (include stems) Artichokes Green bananas Chicory root Radicchio Carrots Radishes Tomatoes Dandelion root Parsnips Ginger Lemon Turmeric Coconut oil Ground raw flax seed