Bifidobacterium animalis subsp. lactis A12 prevents obesityassociated dyslipidemia by modulating gut microbiota-derived short-chain fatty acid production and energy metabolism in high-fat diet-fed mice

  • Tong Li Food Science and Engineering College, Beijing University of Agriculture
  • Jianjun Yang Food Science and Engineering College, Beijing University of Agriculture
  • Hongxing Zhang Food Science and Engineering College, Beijing University of Agriculture
  • Yuanhong Xie Food Science and Engineering College, Beijing University of Agriculture
  • Hui Liu Food Science and Engineering College, Beijing University of Agriculture
  • Jianhua Ren College of Bioengineering, Beijing Polytechnic
  • Fazheng Ren Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University
  • Junhua Jin Food Science and Engineering College, Beijing University of Agriculture, Beijing Laboratory of Food Quality and Safety, Beijing Key Laboratory of Detection and Control of Spoilage Organisms and Pesticide Residues in Agricultural Products
Keywords: Bifidobacterium; Obesity; Short chain fatty acids; Gastrointestinal hormone; Gut microbiota


Background: Bifidobacterium lactis A12 (B. lactis A12) has been shown to have the potential to prevent obesity. However, the mechanisms by which it affects the control of energy metabolism have not been fully elucidated.

Objective: The present work aimed to clarify the mechanisms by that B. lactis A12 has an effect on the management of energy metabolism.

Design: Three- to five-week-old male C57BL/6J mice were randomly divided into five groups, 15 mice for each group. Low-fat diet (LFD) group and high-fat diet (HFD) group were fed with phosphate-buffered saline (PBS) on a daily basis. Cell-free supernatant (CFS), A12, and B. lactis BB12 (BB12) groups were fed with daily probiotics for 10 weeks (1 × 109 CFU of every strain).

Results: The results showed that A12 effectively alleviated relieved weight gain and dyslipidemia, inhibited liver adipose accumulation, and improved leptin resistance in HFD-fed mice (p < 0.05). The anti-obesity effects of B. lactis A12 were closely related to the assembly of short-chain fatty acids (SCFAs), SCFA-downstream receptors, and glucagon-like peptide-1 (GLP-1) secretion. Additionally, high-throughput sequencing of the 16S rRNA showed that B. lactis A12 supplementation reversed HFD-induced gut microbiota dysbiosis, which was possible related to the augmented abundance of SCFA-producing bacterium and a minimized ratio of Bacteroidetes to Firmicutes in mice.

Conclusions: B. lactis A12 prevents obesity in some pathways, including the downregulation of sterol regulatory element binding protein-1 mRNA levels in the liver, modulation of the structure of gut microbiota in a gut microbiota-dependent manner, and the upregulation of the SCFA-producing bacteria-related G protein-coupled receptor 43 pathway.


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Hadrich F, Sayadi S. Apigetrin inhibits adipogenesis in 3T3-L1 cells by downregulating PPARγ and CEBP-γα. Lipids Health Dis 2018; 17: 95. doi: 10.1186/s12944-018-0738-0

Haslam DW, James WP. Obesity. Lancet 2005; 366: 1197–209. doi: 10.1016/S0140-6736(05)67483-1

Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 2014; 311: 74–86. doi: 10.1001/jama.2013.281361

Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med 2017; 376: 254–66. doi: 10.1056/NEJMra1514009

Tian P, Li B, He C, Song W, Hou A, Tian S, et al. Antidiabetic (type 2) effects of Lactobacillus G15 and Q14 in rats through regulation of intestinal permeability and microbiota. Food Funct 2016; 7: 3789–97. doi: 10.1039/c6fo00831c

Sato J, Kanazawa A, Ikeda F, Yoshihara T, Goto H, Abe H, et al. Gut dysbiosis and detection of ‘live gut bacteria’ in blood of Japanese patients with type 2 diabetes. Diabetes Care 2014; 37: 2343–50. doi: 10.2337/dc13-2817

Gomes AC, Bueno AA, de Souza RG, Mota JF. Gut microbiota, probiotics and diabetes. Nutr J 2014; 13: 60. doi: 10.1186/1475-2891-13-60

Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, De Vos WM, et al. The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes Metab 2012; 14: 112–20. doi: 10.1111/j.1463-1326.2011.01483.x

Yadav H, Lee JH, Lloyd J, Walter P, Rane SG. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem 2013; 288: 25088–97. doi: 10.1074/jbc.M113.452516

Bagarolli RA, Tobar N, Oliveira AG, Araújo TG, Carvalho BM, Rocha GZ, et al. Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice. J Nutr Biochem 2017; 50: 16–25. doi: 10.1016/j.jnutbio.2017.08.006

Li K, Tian P, Wang S, Lei P, Qu L, Huang J, et al. Targeting gut microbiota: Lactobacillus alleviated type 2 diabetes via inhibiting LPS secretion and activating GPR43 pathway. J Funct Foods 2017; 38: 561–70. doi: 10.1016/j.jff.2017.09.049

Russell DA, Ross RP, Fitzgerald GF, Stanton C. Metabolic activities and probiotic potential of bifidobacteria. Int J Food Microbiol 2011; 149: 88–105. doi: 10.1016/j.ijfoodmicro.2011.06.003

Zuo F, Yu R, Feng X, Chen L, Zeng Z, Khaskheli GB, et al. Characterization and in vitro properties of potential probiotic Bifidobacterium strains isolated from breast-fed infant feces. Ann Microbiol 2016; 66: 1027–37. doi: 10.1007/s13213-015-1187-x

Moya-Pérez A, Neef A, Sanz Y. Bifidobacterium pseudocatenulatum CECT7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in high-fat diet-FedMice. PLoS One 2015; 10: e0126976. doi: 10.1371/journa-l.pone.0126976

Li T, Yang J, Zhang H, Xie Y, Jin J. Bifidobacterium from breastfed infant faeces prevent high-fat-diet-induced glucose tolerance impairment, mediated by the modulation of glucose intake and the incretin hormone secretion axis. J Sci Food Agric 2020; 100: 3308–18. doi: 10.1002/jsfa.10360

Ma J, Ren P, Ren Y Jin J, Liu H. Study on intestinal dynamic distribution of Bifidobacterium lactis A12 and its effect on constipation relief. J Beijing Agricult Univ 2021; 36: 114–20. doi: 10.13473/j.cnki.issn.1002-3186.2021.0320

Xiao S, Zhang Z, Chen M, Zou J, Jiang S, Qian D, et al. Tang ameliorates dyslipidemia in high-fat diet-induced obese rats via elevating gut microbiota-derived short chain fatty acids production and adjusting energymetabolism. J Ethnopharmacol 2019; 241: 112032. doi: 10.1016/j.jep.2019.112032

Wei S, Chen Y, Chen M. Selecting probiotics with the abilities of enhancing GLP-1 to mitigate the progression of type 1 diabetes in vitro and in vivo. J Funct Foods 2015; 18: 473–486. doi: 10.1016/j.jff.2015.08.016

Goossens D, Jonkers D, Russel M, Stobberingh E, Van Den Bogaard A, et al. The effect of Lactobacillus plantarum 299v on the bacterial composition and metabolic activity in faeces of healthy volunteers: a placebo-controlled study on the onset and duration of effects. Aliment Pharmacol Ther 2003; 18: 495–505. doi: 10.1046/j.1365-2036.2003.01708.x

Amato KR, Yeoman CJ, Kent A, Righini N, Carbonero F, Estrada A, et al. Habitat degradation impacts black howler monkey (Alouatta pigra) gastrointestinal microbiomes. ISME J 2013; 7: 1344–53. doi: 10.1038/ismej.2013.16

Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003; 278: 11312–19. doi: 10.1074/jbc.M211609200

Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 2003; 278: 25481–89. doi: 10.1074/jbc.M301403200

Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun 2013; 4: 1829. doi: 10.1038/ncomms2852

Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012; 61: 364–71. doi: 10.2337/db11-1019

Drucker DJ. The biology of incretin hormones. Cell Metab 2006; 3: 153–65. doi: 10.1016/j.cmet.2006.01.004

Belguesmia Y, Domenger D, Caron J, Dhulster P, Ravallec R., Drider D, et al. Novel probiotic evidence of lactobacilli on immunomodulation and regulation of satiety hormones release in intestinal cells. J Funct Foods 2016; 24: 276–86. doi: 10.1016/j.jff.2016.04.014

Sun M, Wu T, Zhang G, Liu R, Sui W, Zhang M, et al. Lactobacillus rhamnosus LRa05 improves lipid accumulation in mice fed with a high fat diet via regulating the intestinal microbiota, reducing glucose content and promoting liver carbohydrate metabolism. Food Funct 2020 Nov 18; 11(11): 9514–25. doi: 10.1039/d0fo01720e

Feng Q, Chen WD, Wang YD. Gut microbiota: an integral moderator in health and disease. Front Microbiol 2018; 9: 151. doi: 10.3389/fmicb.2018.00151

Makki K, Deehan EC, Walter J, Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 2018; 23: 705–15. doi: 10.1016/j.chom.2018.05.012

Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol 2019; 15: 261–73. doi: 10.1038/s41574-019-0156-z

Larraufie P, Martin-Gallausiaux C, Lapaque N, Dore J, Gribble FM, Reimann F, et al. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci Rep 2018; 8: 74. doi: 10.1038/s41598-017-18259-0

Aoki R, Kamikado K, Suda W, Takii H, Mikami Y, Suganuma N, et al. A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation. Sci Rep 2017; 7: 43522. doi: 10.1038/srep43522

Ishizuka A, Tomizuka K, Aoki R, Nishijima T, Saito Y, Inoue R, et al. Effects of administration of Bifidobacterium animalis subsp. lactis GCL2505 on defecation frequency and bifidobacterial microbiota composition in humans. J Biosci Bioeng 2012; 113: 587–91.

Lee T, Schwandner R, Swaminath G, Weiszmann J, Cardozo M, Greenberg J, et al. Identification and functional mcharacterization of allosteric agonists for the G protein-coupled receptor FFA2. Mol Pharmacol 2008; 74: 1599–609. doi: 10.1124/mol.108.049536

Madsbad S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics) – preclinical and clinical results. Best Pract Res Clin Endocrinol Metab 2009; 23: 463–77. doi: 10.1016/j.beem.2009.03.008

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444: 1027–31. doi: 10.1038/nature05414

Schwiertz A, Taras D, Schäfer K, Beijer S, Bos NA, Donus C, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 2010; 18: 190–5. doi: 10.1038/oby.2009.167

Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 2008; 88: 894–99. doi: 10.1093/ajcn/88.4.894

Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480–4. doi: 10.1038/nature07540

Aron-Wisnewsky J, Prifti E, Belda E, Ichou F, Kayser BD, Dao MC, et al. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut 2019; 68: 70–82. doi: 10.1136/gutjnl-2018-316103

Xie R, Sun Y, Wu J, Huang S, Jin G, Guo Z, et al. Maternal high fat diet alters gut microbiota of offspring and exacerbates DSS-induced colitis in adulthood. Front Immunol 2018; 9: 2608. doi: 10.3389/fimmu.2018.02608

Zhou D, Fan JG. Microbial metabolites in non-alcoholic fatty liver disease. World J Gastroenterol 2019; 25: 2019–28. doi: 10.3748/wjg.v25.i17.2019

Zagato E, Pozzi C, Bertocchi A, Schioppa T, Saccheri F, Guglietta S, et al. Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. Nat Microbiol 2020; 5: 511–24. doi: 10.1038/s41564-019-0649-5

Tap J, Furet JP, Bensaada M, Philippe C, Roth H, Rabot S, et al. Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults. Environ Microbiol 2015; 17: 4954–64. doi: 10.1111/1462-2920.13006

Liu H, Zhang H, Wang X, Yu X, Hu C, Zhang X, et al. The family Coriobacteriaceae is a potential contributor to the beneficial effects of Roux-en-Y gastric bypass on type 2 diabetes. Surg Obes Relat Dis 2018; 14: 584–93. doi: 10.1016/j.soard.2018.01.012
How to Cite
Li T., Yang J., Zhang H., Xie Y., Liu H., Ren J., Ren F., & Jin J. (2022). <em>Bifidobacterium animalis </em&gt;subsp. lactis A12 prevents obesityassociated dyslipidemia by modulating gut microbiota-derived short-chain fatty acid production and energy metabolism in high-fat diet-fed mice. Food & Nutrition Research, 66.
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