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TRI
The Microbiome and Human Metabolism
Karen D. Corbin, PhD, RDInvestigator
Translational Research Institute for Metabolism and Diabetes
TRIOutline
Career Trajectory
Microbiome
• Human Metabolism
• Technological Advances
The Scientist of Tomorrow
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TRITranslational Research Institute for Metabolism and Diabetes
• Dedicated translational research space @ Florida Hospital, Orlando• Mission: Innovate, Discover, Cure• Formula for Success:
• Facilities• Research Niche• Built‐In Synergy• Diversified research portfolio
TRIDefinitions: The “Bugs” that Inhabit Us
Microbiota: A microbial community that occupies a given habitat.
Microbiome: The collective genomes of those microorganisms.
Nutr Rev. 2012; 70:S38
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TRIHumans as Superorganisms: We are not Alone
The human body has 10 times more bacterial than human cells.
Bacteria make up 1‐3% of our body mass.
The Microbiome: The Second Human Genome?
Nature, June 14, 2012, Cover ImageNIH Human Microbiome Project
TRI
Tissue Specificity of Human Microbial Communities
Nat Rev Genet. 2012 13:260
Hair
Nostril
Skin
Vagina
Mouth
Esophagus
H. pylori (‐) stomach
H. pylori (+) stomach
Colon
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TRIFactors that Influence Microbiome Composition
Infancy:• Mode of delivery• Genetics• Breast milk vs. formula
Childhood• Developing immune system
• Socialization• Diet Quality• Antibiotics
Nat Rev Microbiol. 2011;9:279
Adolescence/Early Adulthood:• Puberty• Sexual Activity• Smoking• Moving • Fitness• Diet Experimentation
Adulthood• Weight Gain• Pregnancy• Medication/Illness• Travel• Aging
TRIThe “Aha!” Moment: The Microbiome and Obesity
Germ‐free (GF) mice have smaller fat cells than conventional mice.
When GF mice are exposed to microbiome from conventionally raised mice:
• 60% increase in fat cell size
• Insulin resistance
Why?
• Increased harvest of calories from food
• Increased fat production in liver
• Suppression of a gene that regulates
fat cell size.
PNAS 2004;101:15718
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TRI
Obese adults and adolescents have alterations in the ratio of two bacterial
phyla: Firmicutes and Bacteriodetes.• Proportions shift with weight loss, caloric restriction and bariatric surgery.– Nature. 2006; 444:1022
– Nature. 2009; 457:480
Mice become obese when they receive microbiome from obese, but not lean, twins.
– Science. 2013;341:1241214
Human Obesity: The Role of the Microbiome
N = 11‐12 obese individuals on a weight loss dietvs.
N = 2 lean individuals, 2 samples each, 1 year apart
TRI
Acta Diabetol. 2011. 48:257
Microbial Imbalance (Dysbiosis) & Human Disease
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TRIHow is the Microbiome Linked
to Human Metabolism?
Bile Acids
Energy Harvest
Satiety
Food Intake
Tissue Metabolism
Mitochondrial Function
Aliment Pharmacol Ther; 2015 PMID: 26304302 Nature 2012; 489:242
TRIMicrobiome to Make Space Food?
https://www.npr.org/sections/thesalt
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TRITracking Bacteria in the Human Gut
When bacteria are used therapeutically, how do we know they reached their destination?
A study in mice combined genetic engineering and ultrasound to find out.
• Pilot data indicates this may work in humans. E. coli bacterium that was genetically engineered to
express gas vesicles in order to track its movement through a mouse's body using ultrasound.
https://spectrum.ieee.org/the‐human‐os/biomedicalNature Electronics (2018) 1:79–87
TRIThe State of Microbiome Therapeutics
Microbiome transplants used successfully to treat a bacterial infection (C. diff) that causes gastrointestinal problems.
Preliminary data shows the potential microbiome transplants to treat metabolic disease.
Several companies are actively pursuing microbiome modulating drugs.
N Engl J Med 2013; 368:407; Gut Microbes 2017; 8:253; http://www.secondgenome.com/
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TRIThe Domains of Microbiome Therapeutics
Sci Transl Med. 2011; 3:78ps12.
Healthy Microbiota
Dysbiotic(diseased) microbiota
Diagnosis
Treatment
TRIFilling the Gaps: How Do We Get There?
Move beyond associations and define causality
• Understand the bugs
• Impact of host factors
• Mechanisms
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TRIMicrobiome Studies at TRI
1. Is the microbiome a causal element in human obesity?
2. How is the microbiome modulated in type 1 diabetes as body weight increases?
3. Is the microbiome a biomarker for liver disease resolution after bariatric surgery?
TRIThe Scientist of Tomorrow
Fearless
Outside the Box
Globally Collaborative
Beyond Self
Strong Communicator
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