Updates on the Microbiome: Impacts of current research on nutrition and health. Tiffany Weir, PhD Colorado State University

Learning Objectives Review some of the functions of the microbiome and health issues that are associated with its disruption. Overview  the current knowledge related to dietary components and  the gut microbiota. Evaluate new research and recommendations regarding diet and supplement use for improvements in gut health. 

The Gut Microbiome Am J Gastroenterol Suppl (2012) 1:15–21

Protective functions Curr Opin Microbiol 14:82-91, 2011

Digestion Germ-free mice required 30% more calories to maintain same weight as normal littermates Germ-free mice transplanted with normal microflora gained weight. Increased energy harvest associated with higher levels of the phylum Firmicutes * Turnbaugh and Backhed studies from Gordon lab (2006)

Metabolism: “The SCFA paradox” Intestinal transit acetate leptin

Immune System Priming and Development Hevia et al. 2015 Front. Microbiol

Diet, Disease, and the Microbiota Connection Singh et al. 2017. J Transl. Med.

Sheflin et al. (2014) Curr . Oncol. Reports 16: 406.

Gut Microbiota and Intestinal Disease Awarded the 2005 Nobel Prize in Medicine for their observations that peptic ulcer was caused by the bacteria, Helicobacter pylori. Barry Marshall Robin Warren

H. pylori, peptic ulcers, and gastric cancer 50% of the population has H. pylori as part of normal gut ecology 80% of these remain asymptomatic Some strains have the Cag pathogenicity island Encodes ~30 genes that encode proteins which allow the bacteria to infect the host.

Inflammatory Bowel Disease Increased facultative anaerobes More Adherent invasive E. coli (AIEC) More sulfate reducing bacteria Reduced tryptophan metabolizing bacteria Reduced Faecalibacterium prausnitzii (butyrate producers)

Metabolic Syndrome

Vascular dysfunction: Preclinical manifestation of CVD

*Antibiotics improves vascular function in overweight mice. *Microbiota transplant from genetically obese animals causes vascular dyfunction in normal mice.

Gut Microbiome and Cardiovascular Disease Nature Med 19, 576-585 (2013); Nature Med 19, 533-534 (2013)

Macronutrient Composition, Dietary Patterns, Phytochemicals and the Gut Microbiota

Protein Overall- increased diversity

Fats

Carbohydrates Gazzaniga and Kasper (2016) Cell: based on data from Desai et al. (2016) Cell

Carbohydrates

Phytochemicals

Plant Estrogens 8-prenylnaringenin (8PN) Most potent phytoestrogen to date Bioavailability of 8PN associated with gut microbiota Isoxanthohumol (IX) is converted by gut bacteria to 8-prenylnaringenin (8PN) No 8PN production in germ free rats (Possemiers 2008) Gut bacteria and liver microsomes convert IX to 8PN Resveratrol (a polyphenol) shown to alter gut bacteria community structure Hamm and Weir (2017) Acta Horticulturae

Diet Patterns and the Microbiota

Diet and Development Voreades et al (2014) Frontiers in Microbiology 5:494

Plant –based Diets Stool samples from 60 different mammalian Species showed that their microbiota clustered by dietary pattern. Red: carnivore Blue: omnivore Green: herbivore Ley et al (2008) Science 320: 1647–1651.

Diet and Microbiota Diet De Filipo (2010)PNAS 107 ,14691-14696

Popular Dietary Patterns

“Eat Food. Not Too Much. Mostly Plants.” Summary “Eat Food. Not Too Much. Mostly Plants.” Michael Pollan “In Defense of Food”

Where are we going from here?

Fecal Transplants Frozen fecal matter encapsulated in clear, 1.6 g synthetic pills was just as safe and effective as traditional fecal transplant techniques at treating C. difficile. Within 8 weeks or less, 18 out of 20 participants saw a complete resolution of diarrhea after consuming 30 or 60 of the feces-filled capsules. “It’s probably not the best experience of your life,” says team leader Ilan Youngster, a pediatric infectious disease doctor at Harvard University. “But it beats getting a tube stuck down your throat or a colonoscopy … or having C. diff.” JAMA 10/11/14

C-section Colonization Protocol Dominguez-Bello et al. 2016, Nature Medicine

Functional Medicine and Personalized Nutrition

Diagnostics

Custom Health Solutions based on Knowledge of the Microbiome Enterome-French company that uses mechanistic studies of the microbiome and disease to create custom therapeutic solutions. http://www.enterome.com/ Recombinant Lactic Acid Bacteria- genetically engineered probiotics Metabolically active bacteria would deliver molecules directly to enterocytes. Il-10, protease inhibitors Microbial metabolites as custom pharmaceuticals Supplementation with butyrate, indoles, etc