Effect of Westernized/Globalized diets on Asian gut microbial community

12

5

69

37

12

4

8

10

13

14

1517

18

20

21

22

25

27

28

29

31

32

33

35

36

153

0.02

Lachnospiraceae

Bifidobacteriaceae

Prevotellaceae

Bacteroidaceae

Veillonellaceae

Ruminococcaceae

15776

37

Actinomycetes

1130

Yuan-Kun LeeDepartment of Microbiology, Yong Loo Lin School of Medicine

National University of Singapore

Japan

Taiwan

Indonesia

China

Thailand

Indonesia

Children (7-11 y)

Infant(0 – 3 y)Adult

(20-40 y)Senior (> 60 y)

Mongolia

Korea

Malyasia

Singapore Phillipine

Bifidobacteriaceae

Bacteroidaceae

Lachnospiraceae

Ruminocaccaceae

Beijing

Tokyo

Taipei

Bangkok

Yogyakarta

PC1 (43.0%)

PC2 (21.4%)

Lanzhou

Fukuoka

Taichung

Khon Kaen

Bali

-2

-1

0

1

2

3

4

-2 -1 0 1 2 3 4Prevotellaceae

4

3

2

1

0

-1

-2

- 2 - 1 0 1 2 3 4- 2 - 1 0 1 2 3 4

BB P

4

3

2

1

0

-1

-2

Prediction.strength=0.90Silhouette = 0.313

P-enterotype

BB-enterotype

BeijingLanzhouTokyoFukuokaTaipeiTaichungBangkokKhon KaenYogyakartaBali

rela

tive

ab

un

dan

ce (

%)

0

10

20

30

40

50

60

70

80

90

100PC1

Bacteroidaceae

LachnospiraceaeRuminococcaceae

Prevotellaceae

Bifidobacateriaceae

Asian Microbiome Project (AMP) Phase IPCA and clustering of fecal microbiota of 303 Asian children, 7-11 yr(at family level)

IRuminococcus obeumGemmiger formicilisClostridium clostridioformeBlautia wexleraeEubacterium hadrumBacteroides vulgatusBifidobacteriumpseudocatenulatumBifidobacterium longumClostridium mayombeiBacteroides uniformisBacteroides ovatusEubacterium ventriosumClostridium bartlettiiEggerthella lentaPhascolarctobacterium faeciumDorea formicigeneransDorea longicatenaClostridium nexileEscherichia coli Coprococcus catusButyricicoccus pullicaecorumBlautia stercorisEubacterium biformePrevotella copriCatenibacterium mitsuokaiDesulfovibrio pigerSutterella stercoricanisDialister succinatiphilusMethylobacterium populiDialister invisus

II

III

IV

-3 -2 -1 0 1 2

Log10(relative abundance %)

Species abundance in 303 Asian children / Differences among countries

“Signature of country in gut microbiota”

Taipei

Taichung

Beijing

Yogjakarta Balli

Bangkok

Khon Kaen

Fukuoka

Lanzhou

Tokyo

China

Thailand

Indonesia

Taiwan

Japan

P-type

BB-type

Distribution of enterotypes in the 10 cities

J Nakayama, K Watanabe, JH Jiang, K Matsuda, SH Chao, P Haryono, O La-ongkham, MA Sarwoko, IN Sujaya, L Zhao, KT Chen, YP 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 (2015) Diversity in gut bacterial community of school-age children in Asia. Scientific Reports, 5:8397/DOI 10.1038/srep08397.

Overrepresenting genes in P/BB and US/Africa

Yatsunenko et al., 2012, NatureBB-type P-type

AMP

US Malawi

0.3985 0.1519 0.243 0.2404 0.0861 0.1697 0.1724 0.2789 0.4823 0.1478 0.434 0.1176 0.3259 0.6018 0.5639 0.4415 0.2705 0.7626 0.7621 1.35 0.8559 0.4336 0.4904 1.01 0.9952 1.7828 1.8369 1.6674 1.5326 0.4323 1.3836 0.9261

0.8399 0.2693 0.3958 0.5014 0.5008 0.4223 0.3526 1.6387 0.8892 0.6422 0.8378 0.6237 0.3285 0.713 0.7802 0.4215 0.971 1.8204 1.1617 2.2709 2.1001 1.0498 1.0954 1.3653 1.6589 2.0397 1.5459 2.3008 2.4254 0.8362 2.8383 1.8881

1.9862 2.238 1.7313 1.7537 1.7642 2.1297 2.029 1.249 1.807 1.8592 1.3361 1.5845 2.0528 1.699 2.2075 1.985 1.7716 1.8728 2.5225 2.7662 2.6549 2.1613 1.9826 1.8874 2.5471 1.8398 2.0404 2.6581 2.9329 1.8401 2.5429 2.4256

0.03 0.0152 0.0246 0.0216 0.0137 0.0221 0.014 0.0211 0.0188 0.0252 0.0406 0.023 0.0217 0.0281 0.0113 0.023 0.0212 0.0476 0.0191 0.0247 0.0106 0.0311 0.0301 0.0265 0.0232 0.0113 0.0105 0.0063 0.0058 0.0211 0.0043 0.0087

0.7413 0.2533 0.1561 0.3155 0.0977 0.1336 0.1569 0.3319 0.0931 0.3692 0.2698 0.291 0.1991 0.3237 0.0701 0.1528 0.0587 0.232 0.0932 0.068 0.0466 0.1241 0.1226 0.4645 0.0386 0.0801 0.0771 0.0913 0.0371 0.1588 0.0777 0.0825

0.7491 0.2526 0.1512 0.2709 0.091 0.1085 0.1185 0.4085 0.3849 0.2325 0.2211 0.3393 0.1929 0.3467 0.0397 0.1484 0.0663 0.211 0.0874 0.0536 0.0117 0.07 0.0881 0.4095 0.0144 0.1608 0.461 0.0136 0.0299 0.2041 0.0398 0.0307

0.3734 0.0726 0.0676 0.1796 0.0601 0.0663 0.1063 0.2731 0.0506 0.2168 0.1637 0.163 0.1568 0.1754 0.031 0.0873 0.018 0.1265 0.0418 0.0438 0.021 0.0412 0.0425 0.046 0.0209 0.0223 0.0105 0.0091 0.0126 0.0815 0.0372 0.021

0.0139 0.0032 0.0098 0.0251 0.0029 0.0087 0.0072 0.0083 0.0057 0.008 0.0213 0.007 0.0092 0.009 0.0078 0.0106 0.0059 0.0074 0.0062 0.0066 0.0017 0.0062 0.0057 0.006 0.0099 0.0009 0.0033 0.0012 0 0.0072 0.0026 0.0007

0.2221 0.03 0.0275 0.0317 0.0266 0.0651 0.0307 0.0313 0.0336 0.0523 0.0487 0.0078 0.0819 0.0589 0.0131 0.0358 0.0127 0.037 0.0206 0.0272 0.0042 0.0234 0.0206 0.0165 0.0104 0.0142 0.0042 0.0036 0.0064 0.0429 0.0033 0.0044

0.3947 0.2595 0.1235 0.235 0.1632 0.1064 0.1616 0.221 0.0909 0.3169 0.1722 0.3003 0.2378 0.1896 0.0361 0.1138 0.0406 0.1893 0.074 0.0554 0.0251 0.0966 0.1119 0.0585 0.0171 0.0317 0.0255 0.0059 0.0214 0.1185 0.0122 0.0236

1.2756 0.3678 0.583 0.8121 0.8281 0.5806 0.7958 0.3986 0.6609 0.8459 0.5911 0.6041 0.5929 0.793 1.1553 1.1428 1.374 1.6278 0.9752 2.2496 2.2744 0.9755 1.0319 1.1485 2.0504 0.9854 1.3842 2.1556 3.8517 0.6755 2.7035 2.2386

0.1179 0.0458 0.0531 0.0444 0.0276 0.0873 0.0188 0.003 0.0318 0.0394 0.0611 0.037 0.0144 0.0565 0.0958 0.0908 0.0249 0.021 0.0327 0.0006 0.0322 0.067 0.0449 0.0351 0.0334 0.0198 0.0191 0.0159 0.0378 0.048 0.0191 0.0242

0.046 0.0313 0.0537 0.09 0.0367 0.034 0.031 0.0335 0.0333 0.0657 0.0999 0.0711 0.0418 0.0463 0.0535 0.0333 0.0854 0.0325 0.0459 0.0284 0.0427 0.052 0.0374 0.0329 0.0165 0.0553 0.0193 0.0148 0.0408 0.0196 0.0102 0.0143

2.5905 2.0257 2.0405 2.6258 2.1954 2.8 2.4545 1.2214 1.9015 2.4143 1.9481 2.5467 2.7353 2.2782 2.421 2.1002 1.7892 1.6285 1.8375 1.5938 1.7409 2.3224 1.8689 2.2613 1.2429 1.2035 1.0682 1.212 1.2767 1.658 1.408 1.3448

0.3894 0.1104 0.271 0.2341 0.1869 0.1271 0.1345 0.824 0.3639 0.2529 0.5341 0.2977 0.2202 0.3708 0.056 0.1009 0.1111 0.1924 0.106 0.0892 0.0917 0.0808 0.2165 0.0763 0.0851 0.5364 0.3103 0.0507 0.0716 0.2531 0.0652 0.0327

0.6976 1.0419 0.6633 0.5728 0.3227 0.3707 0.6167 1.7268 1.2055 0.852 1.868 1.3176 0.7578 1.2476 0.2311 0.345 0.375 0.4022 0.3521 0.0968 0.1876 0.4065 0.2967 0.3393 0.0909 1.0676 0.7545 0.1156 0.1791 0.7444 0.2311 0.1455

0.7589 0.4738 0.302 0.4587 0.6161 0.4948 0.5103 0.5379 0.3587 0.3805 0.4706 1.1287 0.437 0.5673 0.2549 0.3455 0.2859 0.2877 0.2857 0.0987 0.107 0.245 0.652 0.1313 0.4513 0.3244 0.3314 0.1285 0.0863 0.7101 0.1548 0.0782

0.8488 0.1481 0.1962 0.3576 0.4551 0.218 0.2665 0.2807 0.1369 0.3359 0.2123 0.5035 0.2585 0.3396 0.2485 0.2148 0.2756 0.2456 0.1614 0.1446 0.155 0.2599 0.2067 0.4244 0.088 0.1206 0.0905 0.0544 0.0846 0.1981 0.1066 0.0852

0.2843 0.1775 0.1048 0.1642 0.1929 0.1379 0.1561 0.2204 0.0682 0.2044 0.103 0.2431 0.1866 0.2087 0.0332 0.0927 0.0862 0.1418 0.0475 0.0511 0.0357 0.0465 0.0714 0.2674 0.0086 0.0266 0.0058 0.0086 0.0096 0.0684 0.0325 0.0098

0.5833 0.6838 0.4893 0.6123 0.4748 0.5648 0.5233 0.2236 0.3464 0.4748 0.329 0.5016 0.5103 0.4192 0.3995 0.5289 0.4503 0.3526 0.3668 0.2251 0.2567 0.3925 0.4368 0.3959 0.1834 0.2158 0.1809 0.1288 0.1773 0.3697 0.2276 0.1743

0.7006 0.5405 0.5574 0.7362 0.5682 0.678 0.6662 0.3242 0.3564 0.5187 0.3236 0.6013 0.484 0.4303 0.5588 0.474 0.5886 0.3964 0.4404 0.2724 0.327 0.4349 0.5659 0.4178 0.2124 0.2671 0.2583 0.1523 0.1921 0.4793 0.267 0.2223

0.6562 0.5609 0.5749 0.6517 0.5515 0.8542 0.6322 0.2607 0.3802 0.5175 0.4195 0.6903 0.7262 0.542 0.535 0.6171 0.5528 0.4474 0.4788 0.3134 0.3545 0.5568 0.5379 0.5024 0.2351 0.2703 0.2413 0.1478 0.2061 0.5321 0.2827 0.2138

0.5905 0.442 0.531 0.5658 0.5127 0.6025 0.58 0.2995 0.3479 0.4377 0.3693 0.7413 0.5761 0.4086 0.4595 0.4846 0.4798 0.3891 0.3525 0.3051 0.323 0.4454 0.4581 0.4589 0.1979 0.2488 0.2387 0.1683 0.2169 0.3845 0.24 0.1868

1.0675 1.0276 1.0333 1.05 0.7393 1.202 1.1226 1.306 0.8675 0.956 0.923 1.1601 0.8827 1.1077 0.6643 1.1217 0.6345 0.5055 0.5567 0.2303 0.4388 0.6781 0.6643 0.4772 0.2533 0.6976 0.5065 0.2642 0.3572 0.7135 0.3399 0.2747

0.9836 0.4629 0.5725 0.6421 0.5863 0.5571 0.4635 0.5276 0.4487 0.8044 0.7478 0.6598 0.575 0.611 0.3192 0.3721 0.2893 0.5325 0.3464 0.1842 0.1553 0.3621 0.3803 0.2862 0.0915 0.2046 0.1428 0.088 0.1581 0.3338 0.1471 0.1669

amyA, malS; alpha-amylase

gltB; glutamate synthase (NADPH/NADH) large chain

gltD; glutamate synthase (NADPH/NADH) small chain

1-pyrroline-5-carboxylate dehydrogenase

glsA, GLS; glutaminase

gadB, gadA, GAD; glutamate decarboxylase

asdA; aspartate 4-decarboxylase

PRODH; proline dehydrogenase

rocD; ornithine--oxo-acid transaminase

kamA; lysine 2,3-aminomutase

AXY8, FUC95A, afcA; alpha-L-fucosidase 2

SHPK; sedoheptulokinase

SORD, gutB; L-iditol 2-dehydrogenase

pfkA, PFK; 6-phosphofructokinase 1

G6PD, zwf; glucose-6-phosphate 1-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, cbiP; adenosylcobyric acid synthase

cobU, cobT; nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase

choloylglycine hydrolase

paaK; phenylacetate-CoA ligase

supported by Mext Grant-in-Aid for Genome Science, 2013

-2

-1

0

1

2

3

4

-1.5 -1 -0.5 0 0.5 1 1.5 2 2.5 3 3.5 4

BB-typeP-typeBangkokKhon Kaen

AMP Phase 3: Globalization effect on gut microbiota of Thai childrenBangkok vs Khon Kaen

What and how drives BB-enterotype in Thai ??

Western

Japanese

Korean

Vietnam

Isan

Thai Office

Factory

Office worker

Factory worker

0 20 40 60 80 100Ratio (%)

0 2 4 6Total varieties

Office workers in Bangkok eat more international foods than factory workers !!

Type of meal

Bifidobacteriaceae

Lachnospiraceae

Ruminococcaceae

Enterobacteriaceae

P = 0.0313 in 999 permutation

Bacteroidaceae

Redundancy analysis showing correlation between dietary habit and microbiota

Factory worker

Office worker

China

Indoniesa

Japan

Korea

Mongolia

Factory worker

Office worker

-0.4

-0.2

0

0.2

0.4

PC

2

Factory Office

0 1 2 3 4 0 1 2 3 4

P=0.0005R=0.4002

Shift of Thai gut microbiota to Japanese gut microbiota with intake of international diets

Japanese

Factory worker

Officeworker

Take Home Message

• Regardless of regions, modernization-like effect was observed.

• But for this moment, both groups look healthy !? Long term effects?

• Could they respond differently to a probiotic intake?

Acknowledgements for Phase 1 study

Gadjah Mada UniversityEndang S. RahayuPri HaryonoMartinus-Agus Sarwoko

National University of SingaporeYuan-Kun LeeKang-Ting ChenNing- Xin Huang

Yakult Central Institute for Microbiological ResearchKoichi WatanabeKazunori MatsudaTakashi KurakawaHirokazu Tsuji

Udayana UniversityI. Nengah Sujaya China Agricultural University

Liang ZhaoFa-Zheng Ren

National Taiwan UniversityYen-Po ChenMing-Ju Chen

Food Industry Research & Development InstituteHsueh-Hui ChiuChii-Cherng Liao

Khon Kaen UniversityVichai Leelavatcharamas

National Yang Ming UniversityShiou-Huei ChaoYing-Chieh Tsai

Kasetsart UniversityLa-Ongkham OrawanSunee Nitisinprasert

Acknowledgements for Phase 2 study

Yeungnam UniversityYongha ParkRather Irfan AhmadKwang-Ho Choi

Health Sciences University of MongoliaGanbold Enkhzaya

National University of SingaporeLee Hui TingRegina AngAngela LimYow Kok SiangAng Sze Chien

Thailand Institute of Scientific and Technological ResearchPhanphen PhoonlapadachaJaruwan Sitdhipol

Mongolian State University of AgricultureShirchin DemberelJamiyan Dugersuren