Iuns 5th yogurt summit 2017 - yini - sharon donovan

The Gut Microbiota:The Intersection Between Diet and

Health

Sharon M. Donovan, PhD, RD

Department of Food Science & Human NutritionUniversity of Illinois, Urbana, USA

Conflict of Interest Disclosure

Danone Institutes International paid for my travelexpenses to chair the session and present this talk,

but did not influence the content of thepresentation.

Presentation Outline

• What is the human microbiome?

• How do we study the microbiome?– Techniques

– HMP and Metahit

– GF and Gnotobiotics

• What have we learned?

– What factors influence gut microbial communities?

– What diseases are linked to the microbiome?

• Conclusions and future directions

What is the Microbiome?

• The “microbiota” represents the collection of microorganisms living on and in the human body, the majority of which inhabit the gastrointestinal tract• Bacteria, fungi, yeasts, viruses, archaea,

and protozoa • The majority live in our gut, particularly in

the large intestine

• The “microbiome” is the collective genomes of the microbiota• The number of microbial genes is 100- times the number of genes

in the human genome.

We Are Mainly Microbes

Source: Gaby D’Allesandro (American Museum of Natural History)

Microbial Cells(100 trillion)

Human Cells(30 trillion)

Microbial Genes(~2 million)

Human Genes

(23,000)

70% 99%




– HMP and Metahit






How Do We Study the Microbiome?

• These techniques apply unbiased “omics” based approaches• Variable regions of the 16S rRNA• DNA

• In the past, microbial composition had been studied using culture-based methods• Underestimated diversity • Only “grow what we know”

• Over the past decade, our understanding of the composition and diversity of the gut microbiota has been advanced by next generation sequencing approaches

Karlsson et al. Assessing the human gut microbiota in metabolic diseases. Diabetes 2013; 62:3341-3349.

Bacterial Identification using 16S rRNA

Tyler et al. Analyzing the human microbiome: a how to guide for physicians. Am J Gastroenterol 2014; 109: 983-993

• Unique to Bacteria & Archaea

• Present in all bacteria – allows use of “Universal Primers”• Design PCR primers that target

different “variable regions”

• Compare to database of available 16S rRNA sequences

Variable and Conserved regions

Most Commonly used

Zoetendal et al. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 2008;57:1605-1615.

16S rRNAapproaches

O’mics Based Approaches to Microbiome Analysis

Which microbes are there?

What are the microbes doing?

What is there genetic potential?

Hierarchical Organization of Taxonomic Levels (E. coli vs. Humans)

Tyler et al. Analyzing the human microbiome: a how to guide for physicians. Am J Gastroenterol 2014; 109: 983-993

Human Microbiome Sequencing Projects

NIH Human Microbiome Project (FY 2007-2012)

Integrative Human Microbiome Project

(FY 2013-2015)

MetaHit(FY 2008-2012)

2007 2008 2009 2010 2011 2012 2013 2014 2015

Year

NIH-Funded Projects

Human Microbiome Project (HMP): FY 2007-2012http://commonfund.nih.gov/hmp/index

• Funded by NIH• Objective: to develop datasets and tools that the community can use to

evaluate which biological properties of the microbiome and host will yield important new insights in understanding human health and disease.

• Five body sites (15-18 subsites) from 300 young, healthy adults (18-40 yrs)• 6 initiatives for data sets and analytical tools

• Objective: to create integrated longitudinal datasets of biological properties from both the microbiome and host from three different cohort studies of microbiome-associated conditions using multiple "omics" technologies.

• Pregnancy and preterm birth – Virginia Commonwealth University• IBD – Broad Institute and Harvard• Prediabetes – Stanford and Jackson Laboratory

Integrative Human Microbiome Project (iHMP): FY 2013-2015http://hmp2.org/

http://commonfund.nih.gov/hmp/index

http://hmp2.org/

• Funded by European Commission – 13 partners from academia & industry• 8 countries in Europe and China

• Its total cost has been evaluated at more than 21.2 million €• European Commission set an upper limit of 11.4 million €

• Objective: to establish associations between the genes of the human intestinal microbiota and our health and disease.

• Sequenced metagenomes (DNA)• Focused on Inflammatory Bowel Disease (IBD) and Obesity

• Research is continuing to be published from the consortium

Metagenomics of the Human Intestinal Tract (MetaHit): 2008-2012http://www.metahit.eu/index.php?id=410

European-Funded Projects

http://www.metahit.eu/index.php?id=410

Mechanisms of Action Using of Germ-free and Gnotobiotic Animal Models

• Germ-free animals have shown that the gut microbiota are essential for normal gastrointestinal, immune, metabolic and cognitive development and function

“Gnotobiotic”

Karlsson et al. Assessing the human gut microbiota in metabolic diseases. Diabetes 2013; 62:3341-3349.




– HMP and Metahit





• Future directions of microbiome, nutrition and health research

Functions of the Microbiome for Health Maintenance

What Have We Learned? – We have redefined what it means to be

human...

1. “We” are mainly microbes and the microbiome comprises 99% of our “metagenome” • Gut microbiome has 1014 resident microorganisms

2. The microbiome is diverse and representing all 3 domains of life• Microbes, Fungi, Archea

3. The microbiota shows remarkable diversity at different anatomical sites

4. Microbiome function is more highly conserved between sites than microbial composition• Different bacteria can fill the same functional niche

Bacterial Phyla by Anatomical

Site

Cho & Blaser. The human microbiome: at the interface of health and disease. Nature Rev. Gen. 2012; 13: 260

FirmicutesBacteroidetesProteobacteriaActinobacteria

HMP Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486: 207

Microbial Ecosystems have Functional Redundancy Across Body Sites and Individuals

Phyla – Who is there?

Metabolic Pathways – What are they doing?




– HMP and Metahit






Factors that Influence Microbiome Composition

Cresci and Bawden. Gut microbiome: What we do and don’t know. Nutr Clin Prac 2015; 30: 734-746.

Microbiota Change Across the Lifespan

Ottman et al. The function of our microbiota: who is out there and what do they do? Front Cell Inf Micro 2012; 2: 104

Birth

day 1-

6 mos

6 mos –

3 yrs

3 years-adult

Advanced Age

Variability amongIndividuals*

• After age 65, the number of microbial species decreases, and populations are more similar among individuals

* Gender, diet, age, hygiene, body site, antibiotic use

Adapted from: http://learn.genetics.utah.edu/content/microbiome/intro/

Incre

ased

diversity in

child

ho

od

Re

du

ced

div

ers

ity

in e

lde

rly

• Family members and pets

• More complex diet

• By age 3, resembles adult• More stable, but affected by

puberty, pregnancy, menopause

• Early diet• Weaning foods

• Route of delivery

Key Factors Across the Life Span

Dietary Factors Influencing the Microbiome

Singh RK et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med 2017; 15:73

• Dietary patterns, specific nutrients and dietary bioactive components all play significant roles in shaping the gut microbiome

• Microbiome composition, metagenome and metabolome are associated with long-term dietary patterns• Macronutrients (Wu G et al. Science 2011; 334: 105-108)• Vegetarian diets (Wu G et al. Gut 2016; 65: 63-72)

• Dietary alterations can induce large, temporary microbial shifts within 24 h (David et al. Nature 2014; 505:559-563)

• Pre and probiotics are commonly used for microbiome modulation• Yogurt has been relatively understudied in terms of its effects on the

microbiome

Impact of Dietary Protein on Intestinal Microbiota & Health Outcomes


TMAO = trimethylamine N-oxide

Impact of Dietary Fat on Intestinal Microbiota & Host Metabolism





– HMP and Metahit






Diet, Microbiome and Health

• Dysbiosis, or an abnormal microbiota, has been associatedwith diseases across organ systems

• Some cause-and effect relationships have been established with gnotobioticanimals.

• Moderated by host genetics and other environmental factors

• Nutrition, probiotics (and prebiotics) modulate the gut microbiome

• Microbes interact with gut epithelium and host immune system

• Microbial products also influence host physiology (e.g. SCFA, LPS)

Potential Mechanisms – Leaky Gut

• Loss of intestinal barrier function

• Bacterial translocation and LPS in circulation

• Immune activation• Local and systemic

inflammation

Sanz et al. Understanding the role of gut microbiome in metabolic disease risk. Pediatr Res 2015; 77: 236-

Potential Mechanisms – Microbial Metabolites

Sanz et al. Understanding the role of gut microbiome in metabolic disease risk. Pediatr Res 2015; 77: 236-

Healthy Diet High Fat Diet

Potential Mechanisms

• Nutrition, probiotics (and prebiotics) modulate the gut microbiome

• Microbes interact with gut epithelium and host immune system

• Microbial products also influence host physiology (e.g. SCFA, LPS)




– HMP and Metahit






Future Directions• Our knowledge of composition has

rapidly expanded, our understanding of function remains limited

– Relatively small sample sizes – are they representative?

• Longer-term observational studies with detailed metadata and stool samples are needed

• Prospective yogurt intervention with to establish dose and mechanisms of action

Microbiome in Health and Disease

Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. Host-gut microbiota metabolic interactions.Science. 2012; 336 :1262-1267

Iuns 5th yogurt summit 2017 - yini - sharon donovan

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