gut microbiome and health · 1 symposium on ‘our second genome,’ annual meeting of indian...
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1Symposium on ‘Our Second genome,’ Annual meeting of Indian Academy of Sciences, Bhopal, 5-Nov-2016
Gut microbiome and health
Sharmila Mande, Ph.DChief Scientist & HeadBio-Sciences R&DTCS ResearchPune
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Outline
Gut microbiome
Challenges in analyzing microbiome data
What constitutes healthy gut microbiome?
Children and adult guts
Gut microbiome and response to antibiotics and drugs
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Gut microbiome
•Digestion of food•Produce vitamins (B and K)•Bio-availibity of drugs•Resistance to antibiotics•…..
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Gut microbiome and diseases/disorders
“All Disease Begins in the Gut” Hippocrates, Father of Medicine
A healthy and balanced gut microbiome is key to ensuring proper digestive functioning
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Analyzing microbiome data
What microbes are there and what are their relative proportions?
What functional genes do they have?
How do they function?
Majority of microbesare unknown!
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Estimating taxa diversity: Challenge
Segregating reads into species-specific bins / OTUs
Known Sequence DB..................................
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Unknown microbes
-Phyla-Class-Order-Family-Genus-Species
What microbes are there and what are their relative proportions?
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Analyzing microbiome data : Challenges
What functional genes do they have?
Contig assembly Functional characterization
Habitat-specific sequences
Key microbial groups,
interactions
How do they function?
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TCS’ end-to-end Metagenomics Analysis PlatformData Pre-processing Contig Assembly
Remove adaptors and primers;Filter out low-quality sequences
Remove host contamination Assemble reads into contigs and scaffolds
Estimate Taxonomic Diversity
Analyse WGS dataset Analyse 16S dataset
Characterize in Functional Terms
Assign sequences to functional categories (COG, KEGG, PFAM & FIGFAM)
Characterize in Functional Terms
Identify relatedness among metagenomes;Identify habitat specific sequences
Identify key microbial groupsand their interactions
In-house scripts EuDetect, CS-SCORE MetaCAA Grid-Assembly
i-rDNAC16S
SOrt-ITEMS; DiScRIBinATE; ProVIDE; SPHINX; INDUS; TWARIT; BinPairs
COGNIZER; Vikodak
HabiSign Igloo-Plot; Community Analyzer
Compress & Archive Datasets/ Results
Compression algorithms for Fasta and Fastq data formats
Data archival strategies
DELIMINATE; FQC; BIND Multi-level data compression strategy
Platform hosts
22 published algorithms
Patented algorithms:35 (10 granted)
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Gut microbiome: Diversity across various life stages
Front Cell Infect Microbiol. 2012; 2: 104 (2012)
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What constitutes the healthy gut microbiota?
2011
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Infection of the intestinal epithelium by gastrointestinal pathogensVicious cycle of infection and malnutrition
Infection adversely affects nutritional status Malnutrition can predispose to infection.
Presence of pathogens normally absent in the intestines of healthy subjects.
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Birbhum district of West Bengal which is typical ofrural and agricultural setting
Nutritional status and Gut microbiome
2014
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What constitutes the healthy human gut microbiota?
Computational Analysis of Metagenomic data
Quantifying the nutritional status of each child
as nutritional Z-scores
Profiling the taxonomic groups in each
sequenced microbiome
Profiling the functional groups in each
sequenced microbiom
Correlating the abundance of taxonomic/functional groups with the nutritional status of children
Nutritional Z-scoresHeight for age (stunted growth- chronic malnutrition)Weight for age (underweight)Weight for height (Wasting or thinness- acute malnutrition)
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Correlating abundance of Taxonomic Groups with Nutritional Status
G1
G4
Taxonomic markers positively or negatively influencing nutritional status
Healthy markers :Probiotic and/or anti-inflammatory genera
Roseburia, Mitsuokella, Faecalibacterium
Energy harvesters from dietary fiber
Butyrvibrio, Roseburia, Faecalibacterium
CommensalsEubacterium, Dialister
Malnourishment markers :Potential Pathogenic genera
Escherichia, Enterobacter, Shigella, Streptococcus, Veillonella
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Genera Co-occurrence network: Apparently healthy
G4
G1
G4
G1
G1
G4 members (Enterobacter and Streptococcus) associating with commensals/G1 members
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Borderline
Apparently healthy
G4 members associating with each other
G1
G1
G4
G1
G4
G4
G4
G4
G4
G1
G1
G1
G1
G4
G1
G1
G1 G1
G1
G1
G1
Variation of Microbial community with Nutritional status
Variation of Microbial community with decrease in nutritional status
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BorderlineG4
G4
G4
G4
G4
G1
G1
G1 G1
G1
G1
G1
Changes in genera co-occurrence networks with decrease in nutritional status
Severely Malnourished
G4
G4
G4
G4
G1
G1
G1
G1
G1
G1
G1
G4 members Enterobacter joining with other G4 members
Members from three hubs join to form one single hub
Two distinct hubs (or ‘armies’) of genera created, one dominated by G1 members and the other by G4 members
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Gut microbiome & Health status
170 severely malnourished children170 childchild
Food supplements
Increase in beneficial bacteria
ood supplements
18181818188818Prospects for development of probiotics and nutraceuticals
Ready-to-Use Therapeutic Food (RUTF)
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Depends on various factors –
• Life style• Ethnicity• Drug usage• Antibiotic usage• ……
How about Adult Gut microbiome?
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Dec. 2015193 individuals 15 ethnic groups 4 geographies :
Assam, Telangana, Sikkim Manipur
Gut microbiome of adult Indian tribes
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15 ethnic groups 4 geographies
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2013
Gut microbiome & response to Antibiotics and drugs
2016
23Increase in exposure to wide range of drugs/xenobiotics with age probably leads to an increase in the xenobiotic metabolizing potential of the gut microbiome.
2016
Abundance of xenobiotic enzymes produced by gut microbiome varies with age and geography
• 397 individuals from 8 nationalities
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2013
• 275 individuals from 8 nationalities
• Global trend of genes conferring resistance to 240 antibiotics
• Abundance of AR genes (total no. of detected AR genes)
• Diversity of AR (No. of antibiotics against which AR genes detected)
Gut microbiome & Antibiotic resistance
255
Genes conferring resistance to ~ 53 antibiotics detected
267 out of 275 263 out of 275
Global trend of antibiotic resistance genes in gut microflora
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Higher in ChineseHigher in American
Higher in Spanish
cephalosporin fosmidomycin
chloramphenicollincosamide, streptogramin B macrolide
F3H8F5
26Higher abundances but lower diversity of AR genes in Chinese
• Chinese have higher number of genes conferring resistance to the same antibiotic• 35 AR genes (out of 157) found only in the Chinese gut metagenomes
Country specific resistance patterns
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Resistotype 1:243 individuals
(Few Chinese + rest of the world)
Resistotype 2: All Chinese
Resistotype 1 resolved into three sub-clusters
Preferred in US individuals(60% of US)
Individuals could be grouped into four clusters based on the resistance profiles in their gut microbiomes
Two clusters represented groups of gut microbiomes having similar abundances of various AR genes
Preferred in Europeanand Japanese populations
Resistotypes: Individuals with similar resistance profiles
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Novel drug targets
Personalized therapeutics
Probiotics and Nutraceuticals
New diagnostic-biomarkers
Alter gut microbiome(we cannot really change our genome)
Analyze gut microbiome : predisposition to diseases/disorders?
Potential for curing chronic diseases using microbiome information
New era of Translational Medicine
AnlyticsPlatform
PharmaAcademia
Hospitals
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CollaboratorsTCS
Acknowledgements
E-mail : sharmila.mande@tcs.comhttp://www.tcs.com/about/research/researchers/Pages/Sharmila-Mande.aspx
NICED(Kolkata) & THSTI, (Gurgaon)
Dr. G.B. Nair
IASST (Guwahati)Dr. Mojibur KhanDr. R. Talukdar
MDRF (Chennai)Dr. V. Mohan
Copenhagen UniversityDr. Oluf Pedersen
Hinduja Hospital (Mumbai)Dr. Philip Abraham
IGIB, DelhiDr. Rajesh Gokhale
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Thank you
TCS Research, Pune
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