Tiffany Weir PhD Colorado State University SOT Webinar January 2020 The Gut Microbiome What does the gut microbiome do Aids in digestion and metabolism Regulate the immune system Protect against ID: 919383
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Slide1
Microbiome: The Missing Piece in the Diet and Health Puzzle
Tiffany Weir, PhDColorado State UniversitySOT WebinarJanuary 2020
Slide2The Gut Microbiome
Slide3What does the gut microbiome do?
Aids in digestion
and metabolism
Regulate the
immune system
Protect against
foreign microbial
invaders
Modulate signaling
between the gut and brain
Slide4Microbiota and Disease
Slide5How do gut microbes contribute to
disease development?Direct pathogenic effectsOne organism, one diseaseEnergy harvestEctopic deposition of adipose tissue
Production of metabolitesCan be harmful or protective
DysbiosisCan be caused by environmental or genetic factorsIncrease pathogens, decrease protective species
Altered barrier functionActivation of immune responses and inflammatory pathways
Slide6Energy Harvest: Microbiota and Obesity
Slide7Production of metabolites
Dietary components
and host-derived molecules can be metabolized by the microbiota to generate compounds that
positively or negatively impact human health.
Short chain fatty acids- derived from fiber and other microbiota accessible carbohydrates.Organic acids from sugars (such as lactic acid) Amino acid metabolites from protein precursors (
ie.melatonin
, serotonin, indoles, biogenic amines, TMAO).
Secondary bile acids from primary bile salt secretions.
Some metabolites of
interest:
Slide8Gentile and Weir (2018)
Science 362:776-780 Short Chain Fatty Acids
Slide9SCFA
Regulate MetabolismFasting induced adipose factor (FIAF):
Fat burningGlp-1: Slows digestion and stops release of stored glucosePYY: Increases
satietyAMPK activation: Improves insulin sensitivity Stimulate the hypothalamus to centrally regulate appetite
Slide10Butyrate and Epithelial Integrity
Butyrate is used an energy source by colonocytes. Beta-oxidation of butyrate
consumes oxygen and produces metabolites that feed into TCA cycleCreates a state of physiologic hypoxia that activates transcription factor HIF-1aHIF-1a promotes expression and translocation of tight junction proteins
Kelly et al. (2015) Cell
Host-Microbe DOI: 10.1016/j.chom.2015.03.005
Slide11MACs and Mucosa
Slide12MACs
preserve intestinal mucosaGazzaniga
and Kasper (2016) Cell: based on data from Desai et al. (2016) Cell
Slide13Dietary MACs
Some studies suggest that >50g fiber/day are required for protective effects.Current USDA recommendations are 25-30g/dayUS average intake is ~15g/dayMACs are found in fruits and vegetables, whole grains, non-dietary prebiotic supplements
Slide14Secondary Bile Acids
Bile acids remodel the microbial community by favoring bile-tolerant organismsMicrobes produce secondary bile acids.Alter membrane rigidity/increase paracellular permeabilityModify enterohepatic
circulation of bile Regulate lipid /energy metabolism through intestinal receptors (FXR/TGR5)
Slide15Dietary Fats
It is difficult to study the role of dietary fat independent of fiber/protein intake changes.In humans, fat consumption increases bile secretions and a transient increase in circulating lipopolysaccharides has been observed.Studies in high fat diets, such as a ketogenic diet, suggest the microbiota is significantly alteredWhether these effects are beneficial is equivocal
Slide16A Tale of Two Protein Metabolites
IPA in the gut
acts through AHRreceptors to stimulateanti-inflammatory m
olecules and improvebarrier function
TMAO is produced by microbial metabolism ofd
ietary
choline
and
carnitine
.
High
circulating
levels are associated
with risk of
atherosclerosis.
Slide17Protein in the Diet
Overall- increased diversity
Slide18Sheflin
AM et al. Curr Oncol Rep
. 2014
Gut Dysbiosis (Microbial Imbalance)
Insult/injury
LPS
Slide19Adapted
from Sheflin AM et al. Curr Oncol
Rep. 2014
Dysbiosis
and Vascular Dysfunction
WD
Microbial
Dysbiosis
:
Imbalance
between protective and harmful bacteria
Promotes
intestinal barrier dysfunction
LPS
TLR4
Impaired
aPWV
Reduced Endothelium-Dependent Dilation
Slide20Transplanting microbiota from obese to lean mice impairs the gut barrier and
induces vascular dysfunctionBattson
et al. Am J Physiol
Heart. (
2019) https://doi.org/10.1152/ajpheart.00346.2019
Slide21# < 0.05 vs. SD
* < 0.05 vs. All
Battson et al. Am J Physiol
Endocrinol
Metab.
(2018)314:E468-E477
Antibiotics reverses vascular dysfunction
Slide22Take home points:
The gut microbiota is an important component in the promotion or prevention of many chronic diseases.Mechanisms of microbiota-driven disease modulation include:Regulating dietary energy harvestGeneration of microbial metabolites from host-derived or dietary compoundsGut dysbiosis and promotion of systemic inflammation Dietary choices influence the microbiome to predict chronic disease risk
Slide23Collaborators:-Dr. Christopher L. Gentile, Colorado State University
-Dr. Sarah A. Johnson, Colorado State University-Dr. Adam Chicco, UC-Colorado, Anschutz Medical CampusDr. Micah Battson, Metro StateDr. Dustin Lee, US ArmyRaj TrikhaKayl Ecton
Acknowledgements: