Beyond the Scope: An Integrative Gastroenterologist s Approach to Digestive Disorders

Transcription

1 Beyond the Scope: An Integrative Gastroenterologist s Approach to Digestive Disorders Robynne Chutkan, MD, FASGE Digestive Center for Wellness, LLC MedStar Georgetown University Hospital

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3 The real voyage of discovery consists not in seeking new landscapes, but in having new eyes Marcel Proust

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9 C-section Vaginal Allergies Asthma Autoimmune diseases Obesity

10 The developing microbiome

11 5 days of antibiotics

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13 Proton pump inhibitors affect the gut microbiome 2000 patients (PPI users vs. non-users) PPI use associated with a significant decrease in diversity PPI use associated with 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

14 Conclusions Effects of PPIs more prominent than effects of antibiotics Gut 2015

15 Autoimmune diseases

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17 HYGIENE hypothesis

18 Multiple sclerosis

19 Helminths infestation

20 Inflammatory Bowel Diseases Dysregulation of mucosal immune system Inappropriate response to commensal microbes

21 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

22 Antibiotics associated with increased risk of new-onset Crohn's disease Meta-analysis 7,208 IBD patients Pooled odds ratio 1.57 Risk of Crohn s in children most markedly increased All antibiotics except PCN strongly associated with IBD Metronidazole or fluoroquinolones highest risk American Journal of Gastroenterology 2014

23 Rural residence during early life is associated with a lower risk of IBD Rural households have 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 of life Early life exposure to farm animals American J of Gastroenterology 2017

24 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

25 Irritable Bowel Syndrome Most common visceral pain syndrome Abdominal pain + change in bowel habits

26 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

27 An IBS subtype defined by speciesspecific alterations in fecal microbiota Microbiome sequencing: 37 IBS patients (15 IBS-D, 10 IBS-C, 12 alternators) 20 age- and gender-matched controls Microbial signatures for: Colonic transit Depression Microbiota-specific subgroups: High Firmicutes Low Bacteroidetes BMJ 2011

28 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

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31 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

32 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

33 A Tale of Two Cities

34 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 gram-negative bacteria (Bacteroidetes) higher microbial richness more species diversity lower prevalence of pathogenic strains of Enterobacteriaceae high levels of SCFA PNAS 2010

35 Conclusions 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

36 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 had significantly less inflammation in the colon and reduced biomarkers of cancer risk on African diet African group had measurements indicating a dramatic increase in cancer risk after two weeks on the western diet Imperial College, London 2015

37 MACs

38 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

39 Diet rapidly & reproducibly alters human gut microbiome Nature, January 2014

40 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

41 Patient characteristics Age range (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

42 Average Time on Diet in Days Average time on diet Time on Diet (in days) Patient

43 Time on Diet (in Days) Time on diet before improvement Average Time (in Days) Patient

44 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%)

45 Endoscopic Results Colonoscopy in 8 pts 6 out of 8 showed mucosal healing

46 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

47 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

48 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

49 Emphasize these foods Fermented foods Onions Leeks Leafy greens Cruciferous 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

50 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

51 Gut microbial imbalance Nature Reviews Immunology Vol 9, May

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