Lee YK ILSI May 2016 Public PPT.pdf

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Human gut microbiota play critical roles in

rogram c/o Department of Microbiology, Yong

Kazunori Matsuda Takashi Kurakawa Hirokazu

Nengah Sujaya Kasetsart University La-Ongkham

Intestinal micro-environment (host physiology

University Shiou-Huei Chao Ying-Chieh Tsai

Institute Hsueh-Hui Chiu Chii-Cherng Liao

Chen China Agricultural University Liang Zhao

Yuan-Kun Lee Kang-Ting Chen Ning- Xin Huang

European, North American and African Asian

1 Asian an gut g microbiotaa Composition mposition osition n ac across cross age and geograp geography, geo geog implication implica ation ation on and health h iimpact Human gut microbiota play critical roles in health & diseases Actinomycetes 5 7 Bifidobacteriaceae Bif 75 5 Intestinal microbiota profile is determined by: Veillonellaceae Lee Yuan-Kun Asian Microbiome rogram c/o Department of Microbiology, Yong Loo Lin School of Medicine National University of Singapore Asian Human Microbiome initiation: Workshop - December 9 Singapore Yakult Central Institute for Microbiological Research Koichi Watanabe Kazunori Matsuda Takashi Kurakawa Hirokazu Tsuji Gadjah Mada University sity Endang S. Rahayu ri Haryono Martinus-Agus Sarwoko Udayana University I. Nengah Sujaya Kasetsart University La-Ongkham Orawan Sunee Nitisinprasert University Vichai Leelavatcharamas i. Exposure during infancy ii. Ability of the microbe to adhere to intestinal surface: Adhesin-receptor interaction ii. Ability to colonize intestinal surface: Intestinal micro-environment (host physiology stage & dietary habit) National Yang Ming University Shiou-Huei Chao Ying-Chieh Tsai Food Industry Research & Development Institute Hsueh-Hui Chiu Chii-Cherng Liao National Taiwan University Yen-o Chen Ming-Ju Chen China Agricultural University Liang Zhao Fa-Zheng Ren National University of Singapore Yuan-Kun Lee Kang-Ting Chen Ning- Xin Huang Asian diet and life style different from European, North American and African Asian Microbiome roject (AM) hase I Species abundance in Asian children / 5 countries in Asia Signature of country in gut microbiota (MiSeq sequencing) Log(relative abundance %) Ruminococcus obeum I Gemmiger formicilis Clostridium clostridioforme Blautia wexlerae Eubacterium hadrum Bacteroides vulgatus Bifidobacterium pseudocatenulatum Bifidobacterium longum Clostridium mayombei Bacteroides uniformis Bacteroides ovatus Eubacterium ventriosum Clostridium bartlettii Eggerthella lenta hascolarctobacterium faecium Dorea formicigenerans II Dorea longicatena Clostridium nexile Escherichia coli Coprococcus catus Butyricicoccus pullicaecorum Blautia stercoris Eubacterium biforme III revotella copri Catenibacterium mitsuokai Desulfovibrio piger Sutterella stercoricanis Dialister succinatiphilus Methylobacterium populi IV Dialister invisus

2 CA and clusterin clustering of fecal microbiota of Asian children, yr (at family level) Bifidobacateriaceae C (.%) rediction.strength=.9 Silhouette =. Bifidobacteriaceae -enterotype Yogyakarta - C (.%) KK5 /Bif-type Bifido-type 7 KK.5 6 KR9 5 KR5 YK FK Gut microbiome of Asian children across geographical region Random forest clustering of Asian children FK YK6*.5 BL8 Yogyakarta Ruminocaccaceae - FK7 KR Bifidobacterium G bases for 6 samples C -enterotype (HiSeq sequencing) KR relative Confirmed by REAL shotgun n metagenomicc sequence FK FK6 BK9 -.5 FK5 BK5-.5 FK6 FK9 BK BK - BK6 Firmicutes.5 KK7 KK.5 KK6 BL6 BK5 BK8 KK YK YK6 BL5 BL YK YK.5 BL8.5 Strong Mild Clostoridia-type-.5 Bacteroides revotella Gut microbiome of Asian children across geographical region Samples: children aged 7~ years Bifidobacateriaceae -enterotype ercentage = accuracy in random forest clustering Japa Ja pane pa nese se ((97 97%) 97 Japanese (97%) hilippines -enterotype Indo donesi sia (86%) (86% 6%) Indonesia Yogjakarta Dimension Seoul Thailand Indonesia Chinaa (8%) Ch (8% (8 %)) % Bifido/ Bacteroid type () Dimension J Nakayama, K Watanabe, JH Jiang, K Matsuda, SH Chao, Haryono, O La-ongkham, MA Sarwoko, IN Sujaya, L Zhao, KT Chen, Y Chen, HH Chiu, T Hidaka, NX Huang, C Kiyohara, T Kurakawa, N Sakamoto, K Sonomoto, K Tashiro, H Tsuji, MJ Chen, V Leelavatcharamas, CC Liao, S Nitisinprasert, ES Rahayu, FZ Ren, YC Tsai, YK Lee (5) Diversity in gut bacterial community of school-age children in Asia. Scientific Reports, 5:897/DOI.8/srep897. Yogyakarta revotella type ()

6...6.8 Japonica Resistant Starch (.6%) Food intake (Carbohydrate) frequency (per day)..9. Rice << << < > > >> > Wheat...9 > > > < < <<.6 Indica Javanica Resistant Starch (6.

) <: lower than other cities (p<.5); <<: lower than other cities (p<.

3 Japonica Resistant Starch (.6%) Food intake (Carbohydrate) frequency (per day)..9. Rice << << < > > >> > Wheat...9 > > > < < <<.6 Indica Javanica Resistant Starch (6.6%) K76 K75 K87 (alpha-amylase) (alpha-amylase) (alpha-glucosidase) C C C >: higher than other cities (p<.5); >>: higher than other cities (p<.) <: lower than other cities (p<.5); <<: lower than other cities (p<.) Bifidobacateriaceae *ie chart represents contribution of bacteria family to these genes Overrepresentation representation of genes for vitamin biosynthesis and carbohydrate digesting enzymes es (CAZyme me) Vitamins CAZyme Ascorbate Menaquinone Thiamine antothenate Cobalamin Biotin C K B B5 B B7 amylase pectinase redicted metagenome e (ICRUSt St) suggests sts non on-digested amylose in the colon of Difference in microbiota of Vegetarian vs Non- n-vegetarian in Thai population suggests the influence of meat consumption Bacteroides C (5.9%) Nonvegetarian Vegetarian.. revotella C (55.%) Enterobacteriaceae Axis

BaiB BaiB Choloylglycinehydrolase (CGH) bile acid-coenzyme A ligase (BaiA) redicted

7 Abundance (%) of predicted KEGG (Secondary bile acid synthesis) Kill revotella + Less

starch Bile acid in colon romote revotella + bile sensitive species Diversity

synthase (NADH/NADH) large chain gltd; glutamate synthase (NADH/NADH) small chain

decarboxylase asda; aspartate -decarboxylase RODH; proline dehydrogenase rocd;

alpha-l-fucosidase SHK; sedoheptulokinase SORD, gutb; L-iditol -dehydrogenase pfka, FK;

MANBA, manb; beta-mannosidase bioa; adenosylmethionine-8-amino-7-oxononanoate

adenosylcobinamide-phosphate synthase cobb-cbia; cobyrinic acid a,c-diamide synthase

nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase choloylglycine

Filippo, C. et al. roc. Natl. Acad. Sci. U S A 7, 69-696 (). Florence Burkina Faso.

4 No. of observed OTUs Enrichment of genes involved in bile acid metabolism in -enterotype CGH BaiB BaiB Choloylglycinehydrolase (CGH) bile acid-coenzyme A ligase (BaiA) redicted metagenome (ICRUSt USt) suggests high bile acid in the colon of K (choloylglycine hydrolase) C 5 WORKING HYOTHESIS R =.5 < Abundance (%) of predicted KEGG (Secondary bile acid synthesis) Kill revotella + Less resistant starch Bile acid in colon Diversity bile sensitive species High resistant starch Bile acid in colon romote revotella + bile sensitive species Diversity Overrepresenting genes in / and US/Africa Global microbiota profile of children Yatsunenko et al.,, Nature US Malawi Asia Microbiome rogram amya, mals; alpha-amylase gltb; glutamate synthase (NADH/NADH) large chain gltd; glutamate synthase (NADH/NADH) small chain -pyrroline-5-carboxylate dehydrogenase glsa, GLS; glutaminase gadb, gada, GAD; glutamate decarboxylase asda; aspartate -decarboxylase RODH; proline dehydrogenase rocd; ornithine--oxo-acid transaminase kama; lysine,-aminomutase AXY8, FUC95A, afca; alpha-l-fucosidase SHK; sedoheptulokinase SORD, gutb; L-iditol -dehydrogenase pfka, FK; 6-phosphofructokinase G6D, zwf; glucose-6-phosphate -dehydrogenase alpha-mannosidase MANBA, manb; beta-mannosidase bioa; adenosylmethionine-8-amino-7-oxononanoate aminotransferase lipb; lipoyl(octanoyl) transferase cbib, cobd; adenosylcobinamide-phosphate synthase cobb-cbia; cobyrinic acid a,c-diamide synthase cobq, cbi; adenosylcobyric acid synthase cobu, cobt; nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase choloylglycine hydrolase paak; phenylacetate-coa ligase Yatsunenko et al., Nature USA Bifidobacteriaceae Venezuela De Filippo, C. et al. roc. Natl. Acad. Sci. U S A 7, (). Florence Burkina Faso. Heping Zha Sichuan Bangladesh Yogjakarta Korea J Nakayama, K Watanabe, JH Jiang, K Matsuda, SH Chao, Haryono, O La-ongkham, MA Sarwoko, IN Sujaya, L Zhao, KT Chen, Y Chen, HH Chiu, T Hidaka, NX Huang, C Kiyohara, T Kurakawa, N Sakamoto, K Sonomoto, K Tashiro, H Tsuji, MJ Chen, V Leelavatcharamas, CC Liao, S Nitisinprasert, ES Rahayu, FZ Ren, YC Tsai, YK Lee (5) Diversity in gut bacterial community of school-age children in Asia. Scientific Reports 5 : 897 DOI:.8/srep897

hase II/III started in additional partners AM hase I: Distribution of enterotypes in the

University hilippines Julie Tan Ladie Anne alermo n State University of Agriculture Shirchin

University China ; Thailand Institute of Scientific and Technological Research hanphen

Mung Seong Yogjakarta China Thailand Indonesia Balli Japan Taiwan J Nakayama, K Watanabe, JH

Chen, HH Chiu, T Hidaka, NX Huang, C Kiyohara, T Kurakawa, N Sakamoto, K Sonomoto, K

YC Tsai, YK Lee (5) Diversity in gut bacterial community of school-age children in Asia.

AM hase III: Gut microbiota vs What drives -enterotype in Thai & how?? -.5

5 hase II/III started in additional partners AM hase I: Distribution of enterotypes in the cities Yeungnam University Korea Yongha ark Rather Irfan Ahmad Kwang-Ho Choi Visaya Sate University hilippines Julie Tan Ladie Anne alermo n State University of Agriculture Shirchin Demberel Jamiyan Dugersuren Health Sciences University of Ganbold Enkhzaya Southern Medical University China ; Thailand Institute of Scientific and Technological Research hanphen hoonlapadacha Jaruwan Sitdhipol Universiti Sains Malaysia Liong Min Yze Lee Yeong Yeh Wong Mung Seong Yogjakarta China Thailand Indonesia Balli Japan Taiwan J Nakayama, K Watanabe, JH Jiang, K Matsuda, SH Chao, Haryono, O La-ongkham, MA Sarwoko, IN Sujaya, L Zhao, KT Chen, Y Chen, HH Chiu, T Hidaka, NX Huang, C Kiyohara, T Kurakawa, N Sakamoto, K Sonomoto, K Tashiro, H Tsuji, MJ Chen, V Leelavatcharamas, CC Liao, S Nitisinprasert, ES Rahayu, FZ Ren, YC Tsai, YK Lee (5) Diversity in gut bacterial community of school-age children in Asia. Scientific Reports, 5:897/DOI.8/srep897. AM hase III: Gut microbiota vs What drives -enterotype in Thai & how?? Take Home Message Regardless of regions, urbanization-like effect was observed. Which is the healthier enterotype? But for this moment, both groups look healthy!? -

Intestinal microbiota want the Indonesian kids to conserve energy storage (fat)! 5 unique bacterial strains isolated from healthy Indonesia infants identified according to their 6sRNA sequences.

faecium AR-g phosphorylation is coupled to increased transcription of target genes: Real time CR experiment under a 6h influence of EC6 or Rosiglitazone, (A) Adipose differentiation-related protein,

6 Intestinal microbiota want the Indonesian kids to conserve energy storage (fat)! 5 unique bacterial strains isolated from healthy Indonesia infants identified according to their 6sRNA sequences. Co-evolution? E. faecalis accounted for 9-95% of the enterococci, and the remaining were E. faecium AR-g phosphorylation is coupled to increased transcription of target genes: Real time CR experiment under a 6h influence of EC6 or Rosiglitazone, (A) Adipose differentiation-related protein, ADR, (B) Fasting-induced adipose factor, FIA, (C) interleukin-, (D) inhibition by sirna for AR-g (Si-g) on FIAF compared to scrambled (Scr.), (E) FIAF with kinase inhibitors D9859, LY9 & SB58. (F) Western of nuclear extracts stimulated by EC6 with LY9 or SB58 for minutes. Ku7 is shown as loading control. Infants who developed allergy and necrotizing enterocolitis were less often colonized with enterococci during the first month of life as compared to healthy infants. IA and Realtime CR analysis. Ingenuity pathway analysis on E.faecalis treated HCT6 cells. All pathways and genes showed in the figure were significantly (p<.5) regulated in HCT6 cells with the treatment of E. faecalis EC6 for 6h at a MOI of. Experiments were done on - biological replicates and technical replicates. FASTING-INDUCED ADIOSE FACTOR (FIAF) INHIBITS ENZYME LIOROTEIN LIASE (LL). LL CATALYZE RELEASE OF FATTY ACIDS AND TRICYGLEROL FROM CIRCULATING LIOROTEIN IN MUSCLE AND ADIOSE TISSUE. ADIOCYTE DIFFERENTIATION-RELATED ROTEIN (ADR) IS ASSOCIATED WITH THE GLOBULE SURFACE MEMBRANE MATERIAL. THIS ROTEIN IS A MAJOR CONSTITUENT OF THE GLOBULE SURFACE. INCREASE IN MRNA LEVELS IS ONE OF THE EARLIEST INDICATIONS OF ADIOCYTE DIFFERENTIATION IL-, ALSO KNOWN AS HUMAN CYTOKINE SYNTHESIS INHIBITORY FACTOR (CSIF), IS AN ANTI-INFLAMMATORY CYTOKINE. Wang SQ, Hibberd ML, ettersson S, Lee YK. Enterococcus faecalis from Healthy Infants Modulates Inflammation through MAK Signaling athways. LOS One, 9: e975. ARE A, ARONSSON L, WANG SG, GREICIUS G, LEE YK, GUSTAFSSON JA, ETTERSSON S, ARULAMALAM V (8) ENTEROCOCCUS FAECALIS ISOLATED FROM NEWEBORN BABIES REGULATE ENDOGENOUS EROXISOME ROLIFERATOR ACTIVATED RECETORGAMMA (ARG) AND INTERLEUKIN- IN COLONIC EITHELIA CELLS. ROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES USA 5: * Take Home Message & questions Thank you! A balanced gut microbiome maintains the wellbeing of the host. What would happen on the introduction of a different diet and exogenous microbes (probiotics included)?

한국성인에서초기황반변성질환과 연관된위험요인연구

한국성인에서초기황반변성질환과 연관된위험요인연구 한국성인에서초기황반변성질환과 연관된위험요인연구 - - i - - i - - ii - - iii - - iv - χ - v - - vi - - 1 - - 2 - - 3 - - 4 - 그림 1. 연구대상자선정도표 - 5 - - 6 - - 7 - - 8 - 그림 2. 연구의틀 χ - 9 - - 10 - - 11 -