Altschul, S.F., Gish, W., Miller, W., Myers, E.W., and Lipman, D.J., 1990. Basic local
alignment search tool. Journal of Molecular Biology 215: 403–410.
https://doi.org/10.1016/S0022-2836(05)80360-2.
Begley, M., Gahan, C.G.M., and Hill, C., 2005. The interaction between bacteria and
bile. FEMS Microbiology Reviews 29: 625–651.
Berthier, F., and Ehrlich, S.D., 1999. Genetic diversity within Lactobacillus sakei and
Lactobacillus curvatus and design of PCR primers for its detection using randomly
amplified polymorphic DNA. International Journal of Systematic Bacteriology 49:
997–1007.
Di Cagno, R., Coda, R., De Angelis, M., and Gobbetti, M., 2013. Exploitation of
vegetables and fruits through lactic acid fermentation. Food Microbiology 33: 1–
10.
Callahan, B.J., McMurdie, P.J., Rosen, M.J., Han, A.W., Johnson, A.J.A., and Holmes,
S.P., 2016. DADA2: High-resolution sample inference from Illumina amplicon
data. Nature Methods 13: 581–583.
Campbell, C.L., Yu, R., Li, F., Zhou, Q., Chen, D., Qi, C., Yin, Y., and Sun, J., 2019.
Modulation of fat metabolism and gut microbiota by resveratrol on high-fat dietinduced obese mice. Diabetes, Metabolic Syndrome and Obesity: Targets and
Therapy 12: 97–107.
Chen, L., Xu, Y., Chen, X., Fang, C., Zhao, L., and Chen, F., 2017. The maturing
development of gut microbiota in commercial piglets during the weaning
transition. Frontiers in Microbiology 8: 1–13.
Cumbie, C.B., and Hermayer, L.K., 2008. Current concepts in targeted therapies for the
pathophysiology of diabetic microvascular complications. Vascular Health and
Risk Management 55: 823–832.
DeSantis, T.Z., Hugenholtz, P., Larsen, N., Rojas, M., Brodie, E.L., Keller, K., Huber,
T., Dalevi, D., Hu, P., and Andersen, G.L., 2006. Greengenes, a chimera-checked
16S rRNA gene database and workbench compatible with ARB. Applied and
19
Environmental Microbiology 72: 5069–72. https://doi.org/10.1128/AEM.0300605.
Fuller R., 1989. Probiotics in man and animals. Journal of Applied Bacteriology 66:
365–378.
Fusco, V., Quero, G.M., Chieffi, D., and Franz, C.M.A.P., 2016. Identification of
Lactobacillus brevis using a species-specific AFLP-derived marker. International
Journal of Food Microbiology 232: 90–94.
Guo, L.D., Yang, L.J., and Huo, G.C., 2011. Cholesterol removal by Lactobacillus
plantarum isolated from homemade fermented cream in inner Mongolia of China.
Czech Journal of Food Sciences 29: 219–225.
Hamilton, M.K., Ronveaux, C.C., Rust, B.M., Newman, J.W., Hawley, M., Barile, D.,
Mills, D.A., and Raybould, H.E., 2017. Prebiotic milk oligosaccharides prevent
development of obese phenotype, impairment of gut permeability, and microbial
dysbiosis in high fat-fed mice. American Journal of Physiology - Gastrointestinal
and Liver Physiology 312: G474–G487. https://doi.org/10.1152/ajpgi.00427.2016.
Huang, Y., Wang, X., Wang, J., Wu, F., Sui, Y., Yang, L., and Wang, Z., 2013.
Lactobacillus plantarum strains as potential probiotic cultures with cholesterollowering activity. Journal of dairy science 96: 2746–53.
https://doi.org/10.3168/jds.2012-6123.
Joyce, S.A., MacSharry, J., Casey, P.G., Kinsella, M., Murphy, E.F., Shanahan, F., Hill,
C., and Gahan, C.G.M., 2014. Regulation of host weight gain and lipid metabolism
by bacterial bile acid modification in the gut. Proceedings of the National
Academy of Sciences 111: 7421–7426. https://doi.org/10.1073/pnas.1323599111.
Karnik, A.A., Fields, A. V, and Shannon, R.P., 2007. Diabetic cardiomyopathy. Current
Hypertension Reports 9: 467–73.
Kennedy, R., Lappin, D.F., Dixon, P.M., Buijs, M.J., Zaura, E., Crielaard, W.,
O’Donnell, L., Bennett, D., Brandt, B.W., and Riggio, M.P., 2016. The
microbiome associated with equine periodontitis and oral health. Veterinary
Research 47: 49. https://doi.org/10.1186/s13567-016-0333-1.
Kim, D.-H., Jeong, D., Kang, I.-B., Kim, H., Song, K.-Y., and Seo, K.-H., 2017. Dual
function of Lactobacillus kefiri DH5 in preventing high-fat-diet-induced obesity:
direct reduction of cholesterol and upregulation of PPAR-α in adipose tissue.
Molecular Nutrition & Food Research: 1700252.
20
https://doi.org/10.1002/mnfr.201700252.
Klindworth, A., Pruesse, E., Schweer, T., Peplies, J., Quast, C., Horn, M., and
Glöckner, F.O., 2013. Evaluation of general 16S ribosomal RNA gene PCR
primers for classical and next-generation sequencing-based diversity studies.
Nucleic Acids Research 41: 1–11.
Konopka, A., 2009. What is microbial community ecology. ISME Journal 3: 1223–
1230.
Lee, C.J., Sears, C.L., and Maruthur, N., 2019. Gut microbiome and its role in obesity
and insulin resistance. Annals of the New York Academy of Sciences: 1–16.
https://doi.org/ 10.1111/nyas.14107.
Liao, C.-C., Ou, T.-T., Wu, C.-H., and Wang, C.-J., 2013. Prevention of diet-induced
hyperlipidemia and obesity by caffeic acid in C57BL/6 mice through regulation of
hepatic lipogenesis gene expression. Journal of Agricultural and Food Chemistry
61: 11082–11088. https://doi.org/10.1021/jf4026647.
Lim, S.-M., Jeong, J.-J., Woo, K.H., Han, M.J., and Kim, D.-H., 2016. Lactobacillus
sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and
obesity in mice by inhibiting gut microbiota lipopolysaccharide production and
inducing colon tight junction protein expression. Nutrition research 36: 337–48.
https://doi.org/10.1016/j.nutres.2015.12.001.
Liong, M.T., and Shah, N.P., 2005. Acid and bile tolerance and cholesterol removal
ability of lactobacilli strains. Journal of Dairy Science 88: 55–66.
https://doi.org/10.3168/jds.S0022-0302(05)72662-X.
Madani, G., Mirlohi, M., Yahay, M., and Hassanzadeh, A., 2013. How much in vitro
cholesterol reducing activity of lactobacilli predicts their in vivo cholesterol
function? International journal of preventive medicine 4: 404–13.
Masood, M.I., Qadir, M.I., Shirazi, J.H., and Khan, I.U., 2011. Beneficial effects of
lactic acid bacteria on human beings. Critical Reviews in Microbiology 37: 91–98.
https://doi.org/10.3109/1040841X.2010.536522.
McDonald, D., Price, M.N., Goodrich, J., Nawrocki, E.P., Desantis, T.Z., Probst, A.,
Andersen, G.L., Knight, R., and Hugenholtz, P., 2012. An improved Greengenes
taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria
and archaea. ISME Journal 6: 610–618. https://doi.org/10.1038/ismej.2011.139.
Million, M., Angelakis, E., Paul, M., Armougom, F., Leibovici, L., and Raoult, D.,
21
2012. Comparative meta-analysis of the effect of Lactobacillus species on weight
gain in humans and animals. Microbial Pathogenesis 53: 100–108.
https://doi.org/10.1016/j.micpath.2012.05.007.
Miyoshi, M., Ogawa, A., Higurashi, S., and Kadooka, Y., 2014. Anti-obesity effect of
Lactobacillus gasseri SBT2055 accompanied by inhibition of pro-inflammatory
gene expression in the visceral adipose tissue in diet-induced obese mice.
European Journal of Nutrition 53: 599–606.
Ogita, T., Tanii, Y., Morita, H., and Tanabe, S., 2011. Suppression of Th17 response by
Streptococcus thermophilus ST28 through induction of IFN-γ. International
Journal of Molecular Medicine 28: 817–822.
https://doi.org/10.3892/ijmm.2011.755.
Olefsky, J.M., and Glass, C.K., 2010. Macrophages, Inflammation, and Insulin
Resistance. Expert Opinion on Therapeutic Targets 19: 1-28.
https://doi.org/ 10.1146/annurev-physiol-021909-135846.
Orci, L., Cook, W.S., Ravazzola, M., Wang, M., Park, B.-H., Montesano, R., and
Unger, R.H., 2004. Rapid transformation of white adipocytes into fat-oxidizing
machines. Proceedings of the National Academy of Sciences 101: 2058–2063.
https://doi.org/10.1073/pnas.0308258100.
Ormerod, K.L., Wood, D.L.A., Lachner, N., Gellatly, S.L., Daly, J.N., Parsons, J.D.,
Dal’Molin, C.G.O., Palfreyman, R.W., Nielsen, L.K., Cooper, M.A., Morrison, M.,
Hansbro, P.M., and Hugenholtz, P., 2016. Genomic characterization of the
uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic
animals. Microbiome 4: 1–17.
Park, S., Ji, Y., Jung, H.-Y., Park, H., Kang, J., Choi, S.-H., Shin, H., Hyun, C.-K., Kim,
K.-T., and Holzapfel, W.H., 2017. Lactobacillus plantarum HAC01 regulates gut
microbiota and adipose tissue accumulation in a diet-induced obesity murine
model. Applied Microbiology and Biotechnology 101: 1605–1614.
https://doi.org/10.1007/s00253-016-7953-2.
Parvez, S., Malik, K.A., Ah Kang, S., and Kim, H.Y., 2006. Probiotics and their
fermented food products are beneficial for health. Journal of Applied Microbiology
100: 1171–1185.
Reeves, P.G., Nielsen, F.H., and Fahey, G.C., 1993. AIN-93 purified diets for
laboratory rodents: final report of the American Institute of Nutrition ad hoc
22
writing committee on the reformulation of the AIN-76A rodent diet. The Journal of
Nutrition 123: 1939–51.
Russo, L., and Lumeng, C.N., 2018. Properties and functions of adipose tissue
macrophages in obesity. Immunology 155: 407–417.
Sandagdorj, B., Hamajima, C., Kawahara, T., Watanabe, J., and Tanaka, S., 2019.
Characterization of microbiota that influence immunomodulatory effects of
fermented Brassica rapa L. Microbes and Environments 34: 206–214.
https://doi.org/10.1264/jsme2.ME19003.
Sanz, Y., Santacruz, A., and Gauffin, P., 2010. Gut microbiota, obesity and metabolic
disorders. Proceedings of the Nutrition Socoety 69: 434–441.
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W.S., and
Huttenhower, C., 2011. Metagenomic biomarker discovery and explanation.
Genome Biology 12: R60. https://doi.org/ 10.1186/gb-2011-12-6-r60.
Serino, M., Luche, E., Gres, S., Baylac, A., Bergé, M., Cenac, C., Waget, A., Klopp, P.,
Iacovoni, J., Klopp, C., Mariette, J., Bouchez, O., Lluch, J., Ouarné, F., Monsan,
P., Valet, P., Roques, C., Amar, J., Bouloumié, A., et al., 2012. Metabolic
adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut
61: 543–553.
De Smet, I., De Boever, P., and Verstraete, W., 1998. Cholesterol lowering in pigs
through enhanced bacterial bile salt hydrolase activity. The British Journal of
Nutrition 79: 185–94. https://doi.org/10.1079/bjn19980030.
Taguchi, H., Senoura, T., Hamada, S., Matsui, H., Kobayashi, Y., Watanabe, J., Wasaki,
J., and Ito, S., 2008. Cloning and sequencing of the gene for cellobiose 2epimerase from a ruminal strain of Eubacterium cellulosolvens. FEMS
Microbiology Letters 287: 34–40. https://doi.org/10.1111/j.15746968.2008.01281.x.
Tanaka, S., Yamamoto, K., Yamada, K., Furuya, K., and Uyeno, Y., 2016. Relationship
of enhanced butyrate production by colonic butyrate-producing bacteria and
immunomodulatory effects in normal mice fed insoluble fraction of Brassica rapa
L. Applied and Environmental Microbiology 82: 2693-2699.
https://doi.org/10.1128/AEM.03343-15.
Tomaro-Duchesneau, C., Jones, M.L., Shah, D., Jain, P., Saha, S., and Prakash, S.,
2014. Cholesterol assimilation by Lactobacillus probiotic bacteria: an in vitro
23
investigation. BioMed Research International 2014: 380316.
https://doi.org/10.1155/2014/380316.
Tomaro-Duchesneau, C., Saha, S., Malhotra, M., Jones, M.L., Rodes, L., and Prakash,
S., 2015. Lactobacillus fermentum NCIMB 5221 and NCIMB 2797 as cholesterollowering probiotic biotherapeutics: In vitro analysis. Beneficial Microbes 6: 861–
869.
Torriani, S., Felis, E.G., and Dellaglio, F., 2001. Differentiation of Lactobacillus
plantarum, L. pentosus, and L. paraplantarum by recA gene sequence analysis and
multiplex PCR assay with recA gene-derived primers. Applied and Environmental
Microbiology 67: 3450–3454.
Verwaerde, C., Delanoye, A., Macia, L., Tailleux, A., and Wolowczuk, I., 2006.
Influence of high-fat feeding on both naive and antigen-experienced T-cell
immune response in DO10.11 mice. Scandinavian Journal of Immunology 64:
457–466.
Wagner, M., Samdal Steinskog, E.S., and Wiig, H., 2015. Adipose tissue macrophages:
the inflammatory link between obesity and cancer? Expert Opinion on Therapeutic
Targets 19: 527–538.
Wolowczuk, I., Verwaerde, C., Viltart, O., Delanoye, A., Delacre, M., Pot, B., and
Grangette, C., 2008. Feeding our immune system: Impact on metabolism. Clinical
and Developmental Immunology 2008: 639803.
https://doi.org/ 10.1155/2008/639803.
Wouters, D., Grosu-Tudor, S., Zamfir, M., and De Vuyst, L., 2013. Bacterial
community dynamics, lactic acid bacteria species diversity and metabolite kinetics
of traditional Romanian vegetable fermentations. Journal of the Science of Food
and Agriculture 93: 749–760.
Wu, C.-C., Weng, W.-L., Lai, W.-L., Tsai, H.-P., Liu, W.-H., Lee, M.-H., Tsai, Y.-C.,
Wu, C.-C., Weng, W.-L., Lai, W.-L., Tsai, H.-P., Liu, W.-H., Lee, M.-H., and
Tsai, Y.-C., 2015. Effect of Lactobacillus plantarum strain K21 on high-fat dietfed obese mice. Evidence-Based Complementary and Alternative Medicine 2015,
2015: e391767.
Yamamoto, K., Furuya, K., Yamada, K., Takahashi, F., Hamajima, C., and Tanaka, S.,
2018. Enhancement of natural killer activity and IFN-γ production in an IL-12dependent manner by a Brassica rapa L. Bioscience, Biotechnology, and
24
Biochemistry 82: 654–668. https://doi.org/10.1080/09168451.2017.1408396.
Zhao, L., Zhang, Q., Ma, W., Tian, F., Shen, H., and Zhou, M., 2017. A combination of
quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of
gut microbiota. Food and Function 8: 4644–4656.
25
(A)
NFD
35
HFD
30
N07
#4G2
25
20
15
0 2 4 6 8101214
216182022242628
430323436384042
644464850525456
Weeks after feeding
(B)
(C)
Liver (g/100g BW)
Figure 1
NFD
HFD
#4G2
N07
Epididymal adipose tissue (g/100g BW)
Body weight (g)
40
NFD
HFD
#4G2
N07
(A)
(B)
150
100
50
100
50
NFD
Figure 2
HFD
#4G2
N07
250
P=0.104
Serum glucose (mg/dL)
Serum TC (mg/dL)
Serum TG (mg/dL)
150
(C)
NFD
HFD
#4G2
N07
200
P=0.058
150
100
50
NFD
HFD
#4G2
N07
Liver TG (mg/g tissue)
Liver total lipid (mg/g tissue)
300
200
100
NFD
Figure 3
HFD
#4G2
N07
(B)
(C)
200
P=0.147
Liver TC (mg/g tissue)
(A)
150
100
50
NFD
HFD
#4G2
N07
NFD
HFD
#4G2
N07
(A)
(B)
100 µm
(C)
10000
Adipocyte
Adipocytearea
area(mm
(µm2))
(E)
(D)
8000
6000
4000
2000
Figure 4
NFD
HFD
#4G2
N07
Acc1
1.5
Fas
1.5
Acox1
Cpt1
1.5
1.5
Pparg
1.5
Relative expression
1.0
1.0
1.0
1.0
1.0
0.5
0.5
0.5
0.5
0.5
0.0
HFD #4G2 N07
Figure 5
0.0
HFD #4G2 N07
0.0
0.0
HFD #4G2 N07
HFD #4G2 N07
0.0
HFD #4G2 N07
Acc1
Relative expression
2.5
2.0
Fas
2.0
Acox1
Cpt1
1.5
1.0
1.0
1.0
1.0
0.5
0.5
0.5
HFD #4G2 N07
Pparg
2.0
1.5
0.0
HFD #4G2 N07
Ucp1
1.0
0.5
0.0
2.5
2.0
1.5
1.5
1.5
0.0
Relative expression
2.0
HFD #4G2 N07
Figure 6
HFD #4G2 N07
0.0
0.5
HFD #4G2 N07
0.0
HFD #4G2 N07
Relative expression
Tnfa
Il-1b
1.5
1.5
1.0
1.0
Cd11c
F4/80
1.5
2.0
1.5
1.0
1.0
0.5
0.0
0.5
HFD #4G2 N07
Figure 7
0.0
0.5
0.5
HFD #4G2 N07
0.0
HFD #4G2 N07
0.0
HFD #4G2 N07
(B)
50
NFD
HFD
#4G2
N07
0.2
-0.1
NFD
HFD
#4G2
0.1
40
0.1
35
HFD
30
N07
N07
0.0
100
-0.1
-0.2
10
PC2 - Percent variation explained 10.71 %
PCoA - PC1 vs PC2
0.2
-0.2
(C)
PC2 (10.71 %)
Observed OTUs
150
Faith's phylogenetic diversity
(A)
-0.1
(E)
10
NFD
Figure 8
HFD
#4G2
N07
Relative abundance of
f_Lactobacillaceae|_ (%)
Relative abundance of
o_Lactobacillales|f_|g_ (%)
10
NFD
HFD
#4G2
N07
#4G2
0.1
-0.1PC1 - Percent0variation
25explained0.1
28.67 %
PC1 (28.67 %)
(F)
Relative abundance of
f_S24-7|g_ (%)
(D)
0.0
NFD
0.2
0.2
20
15
0 2 4 6 8101214161820222426283
NFD
HFD
#4G2
N07
Table S1. Primer sequences for Lactobacillus species-specific PCR.
Target species
Forward (5¢ ® 3¢)
Reverse (5¢ ® 3¢)
L. brevis
AATTGATTTTCATACCGCAGAA
TTGGCACCGCATGATGTG
L. curvatus
GCTGGATCACCTCCTTTC
TTGGTACTATTTAATTCTTAG
L. plantarum
CCGTTTATGCGGAACACCTA
TCGGGATTACCAAACATCAC
Table S2. Primer sequences for reverse transcription-PCR.
Target gene
Forward (5¢ ® 3¢)
Reverse (5¢ ® 3¢)
Acc1
TGTTGAGACGCTGGTTTGTAGAA
GGTCCTTATTATTGTCCCAGACGTA
Fas
GATCCTGGAACGAGAACACGA
GAGACGTGTCACTCCTGGACTTG
Acox1
CTATGGGATCAGCCAGAAAGG
AGTCAAAGGCATCCACCAAAG
Cpt1
AGACCGTGAGGAACTCAAACCTAT
TGAAGAGTCGCTCCCACT
Pparg
TGACAGGAAAGACAACAGACAAAT
GGGTGATGTGTTTGAACTTGATT
Ucp1
TGCCACACCTCCAGTCATTA
TTGGAGCTGGCTTCTGTGC
Tnfa
TGGGAGTAGACAAGGTACAACCC
CATCTTCTCAAAATTCGAGTGACAA
Il1b
GTGGACCTTCCAGGATGAGG
CGGAGCCTGTAGTGCAGTTG
Cd11c
TGTGACGGTGTCTAATGATGG
AGTTGATGCTGACTGGCACG
F4/80
CCCCAGTGTCCTTACAGAGTG
GTGCCCAGAGTGGATGTCT
Rps18
CAGTGGTCTTGGTGTGCTGA
ACCTGGAGAGGCTGAAGAAA
NFD
HFD
#4G2
N07
Figure S1. Cladogram for differentially abundant gut microbiota of mice fed a normal-fat diet (NFD), high-fat diet (HFD),
HFD supplemented with Lactobacillus curvatus #4G2 (#4G2), and HFD supplemented with Lactobacillus plantarum
Shinshu N-07 (N07) were constructed based on LEfSe analysis. Only taxa meeting an LDA significant threshold >3 are
shown.
...
論文の公開元へ
