Strain-level screening of human gut microbes identifies Blautia producta as a new anti-hyperlipidemic probiotic

References

• Wu P, Feng Q, Kerchberger VE, Nelson SD, Chen Q, Li B, Edwards TL, Cox NJ, Phillips EJ, Stein CM, et al. Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension. Nat Commun. 2022;13(1):46. doi:10.1038/s41467-021-27751-1.
   PubMed Web of Science ®Google Scholar
• Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341–22. doi:10.1038/nri.2016.42.
   PubMed Web of Science ®Google Scholar
• O’Toole PW, Jeffery IB. Gut microbiota and aging. Science. 2015;350(6265):1214–1215. doi:10.1126/science.aac8469.
   PubMed Web of Science ®Google Scholar
• Cani PD. Microbiota and metabolites in metabolic diseases. Nat Rev Endocrinol. 2019;15(2):69–70. doi:10.1038/s41574-018-0143-9.
   PubMed Web of Science ®Google Scholar
• Effendi R, Anshory M, Kalim H, Dwiyana RF, Suwarsa O, Pardo LM, Nijsten TEC, Thio HB. Akkermansia muciniphila and faecalibacterium prausnitzii in immune-related diseases. Microorganisms. 2022;10(12):10. doi:10.3390/microorganisms10122382.
   Web of Science ®Google Scholar
• Liu X, Mao B, Gu J, Wu J, Cui S, Wang G, Zhao J, Zhang H, Chen W. Blautia—a new functional genus with potential probiotic properties? Gut Microbes. 2021;13(1):1875796. doi:10.1080/19490976.2021.1875796.
   PubMed Web of Science ®Google Scholar
• Wu C, Zhao Y, Zhang Y, Yang Y, Su W, Yang Y, Sun L, Zhang F, Yu J, Wang Y, et al. Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR’s cholesterol-decreasing efficacy in patients. J Adv Res. 2022;37:197–208. doi: 10.1016/j.jare.2021.07.011.
   PubMed Web of Science ®Google Scholar
• Whang A, Nagpal R, Yadav H. Bi-directional drug-microbiome interactions of anti-diabetics. EBioMedicine. 2019;39:591–602. doi: 10.1016/j.ebiom.2018.11.046.
   PubMed Web of Science ®Google Scholar
• Tong X, Xu J, Lian F, Yu X, Zhao Y, Xu L, Zhang M, Zhao X, Shen J, Wu S, et al. Structural alteration of gut microbiota during the amelioration of human type 2 diabetes with hyperlipidemia by metformin and a traditional Chinese herbal formula: a multicenter, randomized, open label clinical trial. mBio. 2018;9(3):e02392–17. doi:10.1128/mBio.02392-17.
   PubMed Web of Science ®Google Scholar
• Patnode ML, Guruge JL, Castillo JJ, Couture GA, Lombard V, Terrapon N, Henrissat B, Lebrilla CB, Gordon JI. Strain-level functional variation in the human gut microbiota based on bacterial binding to artificial food particles. Cell Host & Microbe. 2021;29(4):664–673.e5. doi:10.1016/j.chom.2021.01.007.
   PubMed Web of Science ®Google Scholar
• Enav H, Backhed F, Ley RE. The developing infant gut microbiome: a strain-level view. Cell Host & Microbe. 2022;30(5):627–638. doi:10.1016/j.chom.2022.04.009.
   PubMed Web of Science ®Google Scholar
• Kamada N, Inoue N, Hisamatsu T, Okamoto S, Matsuoka K, Sato T, Chinen H, Hong KS, Yamada T, Suzuki Y, et al. Nonpathogenic Escherichia coli strain Nissle1917 prevents murine acute and chronic colitis. Inflamm Bowel Dis. 2005;11(5):455–463. doi:10.1097/01.MIB.0000158158.55955.de.
   PubMed Web of Science ®Google Scholar
• Luo Z, Xie X, Qi Y, Wu Y. Hemolytic Escherichia coli inhibits swarming and differentiation of proteus mirabilis. Curr Microbiol. 2018;75(4):471–475. doi:10.1007/s00284-017-1404-x.
   PubMed Web of Science ®Google Scholar
• Metwaly A, Haller D. Strain-level diversity in the gut: the P. copri case. Cell Host & Microbe. 2019;25(3):349–350. doi:10.1016/j.chom.2019.02.006.
   PubMed Web of Science ®Google Scholar
• Aoki R, Onuki M, Hattori K, Ito M, Yamada T, Kamikado K, Kim Y-G, Nakamoto N, Kimura I, Clarke JM, et al. Commensal microbe-derived acetate suppresses NAFLD/NASH development via hepatic FFAR2 signalling in mice. Microbiome. 2021;9(1):188. doi:10.1186/s40168-021-01125-7.
   PubMed Web of Science ®Google Scholar
• Im D-S. FFA4 (GPR120) as a fatty acid sensor involved in appetite control, insulin sensitivity and inflammation regulation. Mol Aspects Med. 2018;64:92–108. doi: 10.1016/j.mam.2017.09.001.
   PubMed Web of Science ®Google Scholar
• Canfora EE, Meex RC, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019;15(5):261–273. doi:10.1038/s41574-019-0156-z.
   PubMed Web of Science ®Google Scholar
• Versluis D, de J Bello González T, Zoetendal EG, Passel M, Smidt H, Abdo Z. High throughput cultivation-based screening on porous aluminum oxide chips allows targeted isolation of antibiotic resistant human gut bacteria. PLoS One. 2019;14(1):e0210970. doi:10.1371/journal.pone.0210970.
   PubMed Web of Science ®Google Scholar
• Kirtzalidou E, Pramateftaki P, Kotsou M, Kyriacou A. Screening for lactobacilli with probiotic properties in the infant gut microbiota. Anaerobe. 2011;17(6):440–443. doi:10.1016/j.anaerobe.2011.05.007.
   PubMed Web of Science ®Google Scholar
• van de Steeg E, Schuren FH, Obach RS, van Woudenbergh C, Walker GS, Heerikhuisen M, Nooijen IHG, Vaes WHJ. An ex vivo fermentation screening platform to study drug metabolism by human gut microbiota. Drug Metab Dispos. 2018;46(11):1596–1607. doi:10.1124/dmd.118.081026.
   PubMed Web of Science ®Google Scholar
• Koopman N, Molinaro A, Nieuwdorp M, Holleboom AG. Can bugs be drugs? The potential of probiotics and prebiotics as treatment for non‐alcoholic fatty liver disease. Aliment Pharmacol Ther. 2019;50(6):628–639. doi:10.1111/apt.15416.
   PubMed Web of Science ®Google Scholar
• Liu L, Wang Y, Zhang J, Wang C, Li Y, Dai W, Piao C, Liu J, Yu H, Li X, et al. Probiotics in treating with alcoholic liver disease and nonalcoholic fatty liver disease. Food Rev Int. 2021:1–19. doi: 10.1080/87559129.2021.1967380.
   Google Scholar
• Bauer PV, Duca FA, Waise TMZ, Dranse HJ, Rasmussen BA, Puri A, Rasti M, O’Brien CA, Lam TKT. Lactobacillus gasseri in the upper small intestine impacts an ACSL3-dependent fatty acid-sensing pathway regulating whole-body glucose homeostasis. Cell Metab. 2018;27(3):572–87 e6. doi:10.1016/j.cmet.2018.01.013.
   PubMed Web of Science ®Google Scholar
• Kim J, Yun JM, Kim MK, Kwon O, Cho B. Lactobacillus gasseri BNR17 supplementation reduces the visceral fat accumulation and waist circumference in obese adults: a randomized, double-blind, placebo-controlled trial. J Med Food. 2018;21(5):454–461. doi:10.1089/jmf.2017.3937.
   PubMed Web of Science ®Google Scholar
• Yu J, Yang Y, Li Z, Ma Y, Zhao B, Wu C. Research on the lipid-lowering activity of Lactobacillus gasseri. J Chin I Food Sci Technol. 2022;22:72–79.
   Google Scholar
• Benitez-Paez A, Gomez Del Pugar EM, Lopez-Almela I, Moya-Perez A, Codoner-Franch P, Sanz Y, Turnbaugh PJ. Depletion of blautia species in the microbiota of obese children relates to intestinal inflammation and metabolic phenotype worsening. mSystems. 2020;5(2). doi:10.1128/mSystems.00857-19.
   PubMed Web of Science ®Google Scholar
• Hosomi K, Saito M, Park J, Murakami H, Shibata N, Ando M, Nagatake T, Konishi K, Ohno H, Tanisawa K, et al. Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota. Nat Commun. 2022;13(1):1–17. doi:10.1038/s41467-022-32015-7.
   PubMed Web of Science ®Google Scholar
• Ozato N, Yamaguchi T, Mori K, Katashima M, Kumagai M, Murashita K, Katsuragi Y, Tamada Y, Kakuta M, Imoto S, et al. Two blautia species associated with visceral fat accumulation: a one-year longitudinal study. Biology (Basel). 2022;11(2):11. doi:10.3390/biology11020318.
   Google Scholar
• Yang Y-N, Wang Q-C, Xu W, Yu J, Zhang H, Wu C. The berberine-enriched gut commensal Blautia producta ameliorates high-fat diet (HFD)-induced hyperlipidemia and stimulates liver LDLR expression. Biomed Pharmacother. 2022;155:113749. doi: 10.1016/j.biopha.2022.113749.
   PubMed Web of Science ®Google Scholar
• Caballero S, Kim S, Carter RA, Leiner IM, Sušac B, Miller L, Kim GJ, Ling L, Pamer EG. Cooperating commensals restore colonization resistance to vancomycin-resistant enterococcus faecium. Cell Host & Microbe. 2017;21(5):592–602. e4. doi:10.1016/j.chom.2017.04.002.
   PubMed Web of Science ®Google Scholar
• Pathmanathan SG, Lawley B, McConnell M, Baird MA, Tannock GW. Gut bacteria characteristic of the infant microbiota down-regulate inflammatory transcriptional responses in HT-29 cells. Anaerobe. 2020;61:102112. doi: 10.1016/j.anaerobe.2019.102112.
   PubMed Web of Science ®Google Scholar
• Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11(10):577–591. doi:10.1038/nrendo.2015.128.
   PubMed Web of Science ®Google Scholar
• Fedorenko A, Lishko PV, Kirichok Y. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell. 2012;151(2):400–413. doi:10.1016/j.cell.2012.09.010.
   PubMed Web of Science ®Google Scholar
• Nakamura MT, Yudell BE, Loor JJ. Regulation of energy metabolism by long-chain fatty acids. Prog Lipid Res. 2014;53:124–144. doi: 10.1016/j.plipres.2013.12.001.
   PubMed Web of Science ®Google Scholar
• Quan LH, Zhang C, Dong M, Jiang J, Xu H, Yan C, Liu X, Zhou H, Zhang H, Chen L, et al. Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation. Gut. 2020;69(7):1239–1247. doi:10.1136/gutjnl-2019-319114.
   PubMed Web of Science ®Google Scholar
• Eibler D, Seyfried C, Vetter W. Enantioselectivity of anteiso-fatty acids in hitherto uninspected sample matrices. J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1061-1062:233–239. doi: 10.1016/j.jchromb.2017.07.029.
   PubMed Web of Science ®Google Scholar
• Kaneda T. Iso- and anteiso-fatty acids in bacteria: biosynthesis, function, and taxonomic significance. Microbiol Rev. 1991;55(2):288–302. doi:10.1128/mr.55.2.288-302.1991.
   PubMedGoogle Scholar
• Hilgendorf KI, Johnson CT, Mezger A, Rice SL, Norris AM, Demeter J, Greenleaf WJ, Reiter JF, Kopinke D, Jackson PK, et al. Omega-3 fatty acids activate ciliary FFAR4 to control adipogenesis. Cell. 2019;179(6):1289–305 e21. doi:10.1016/j.cell.2019.11.005.
   PubMed Web of Science ®Google Scholar
• Bae M, Cassilly CD, Liu X, Park SM, Tusi BK, Chen X, Kwon J, Filipčík P, Bolze AS, Liu Z, et al. Akkermansia muciniphila phospholipid induces homeostatic immune responses. Nature. 2022;608(7921):168–173. doi:10.1038/s41586-022-04985-7.
   PubMed Web of Science ®Google Scholar
• Kimura I, Ichimura A, Ohue-Kitano R, Igarashi M. Free fatty acid receptors in health and disease. Physiol Rev. 2020;100(1):171–210. doi:10.1152/physrev.00041.2018.
   PubMed Web of Science ®Google Scholar
• Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med. 2005;11(1):90–94. doi:10.1038/nm1168.
   PubMed Web of Science ®Google Scholar
• Quesada-Lopez T, Cereijo R, Turatsinze JV, Planavila A, Cairo M, Gavalda-Navarro A, Peyrou M, Moure R, Iglesias R, Giralt M, et al. The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes. Nat Commun. 2016;7(1):13479. doi:10.1038/ncomms13479.
   PubMedGoogle Scholar
• Paschoal VA, Walenta E, Talukdar S, Pessentheiner AR, Osborn O, Hah N, Chi TJ, Tye GL, Armando AM, Evans RM, et al. Positive reinforcing mechanisms between GPR120 and PPARγ modulate insulin sensitivity. Cell Metab. 2020;31(6):1173–88 e5. doi:10.1016/j.cmet.2020.04.020.
   PubMed Web of Science ®Google Scholar
• Colosimo DA, Kohn JA, Luo PM, Piscotta FJ, Han SM, Pickard AJ, Rao A, Cross JR, Cohen LJ, Brady SF. Mapping interactions of microbial metabolites with human G-Protein-coupled receptors. Cell Host & Microbe. 2019;26(2):273–282.e7. doi:10.1016/j.chom.2019.07.002.
   PubMed Web of Science ®Google Scholar
• Davenport AP, Scully CC, de Graaf C, Brown AJ, Maguire JJ. Advances in therapeutic peptides targeting G protein-coupled receptors. Nat Rev Drug Discov. 2020;19(6):389–413. doi:10.1038/s41573-020-0062-z.
   PubMed Web of Science ®Google Scholar
• Congreve M, de Graaf C, Swain NA, Tate CG. Impact of GPCR structures on drug discovery. Cell. 2020;181(1):81–91. doi:10.1016/j.cell.2020.03.003.
   PubMed Web of Science ®Google Scholar
• Qi G, Zhou Y, Zhang X, Yu J, Li X, Cao X, Wu C, Guo P. Cordycepin promotes browning of white adipose tissue through an AMP-activated protein kinase (AMPK)-dependent pathway. Acta Pharm Sin B. 2019;9(1):135–143. doi:10.1016/j.apsb.2018.10.004.
   PubMed Web of Science ®Google Scholar
• Xu W, Chen T, Pei Y, Guo H, Li Z, Yang Y, Zhang F, Yu J, Li X, Yang Y, et al. Characterization of shallow whole-metagenome shotgun sequencing as a high-accuracy and low-cost method by complicated mock microbiomes. Front Microbiol. 2021;12:12. doi: 10.3389/fmicb.2021.678319.
   Web of Science ®Google Scholar
• Kangale LJ, Raoult D, Ghigo E, Fournier P-E. Chryseobacterium schmidteae sp. nov. a novel bacterial species isolated from planarian Schmidtea mediterranea. Sci Rep. 2021;11(1):1–14. doi:10.1038/s41598-021-90562-3.
   PubMed Web of Science ®Google Scholar
• Xia F, Guo L, Cui P, Xu Q, Huang J, Zhou H, Shen W. A sensitive and accurate GC–MS method for analyzing microbial metabolites short chain fatty acids and their hydroxylated derivatives in newborn fecal samples. J Pharmaceut Biomed. 2023;223:115148. doi: 10.1016/j.jpba.2022.115148.
   PubMed Web of Science ®Google Scholar
• Wu C, Feng J, Wang R, Liu H, Yang H, Rodriguez PL, Qin H, Liu X, Wang D. HRS1 acts as a negative regulator of abscisic acid signaling to promote timely germination of Arabidopsis seeds. PLoS One. 2012;7(4):e35764. doi:10.1371/journal.pone.0035764.
   PubMed Web of Science ®Google Scholar
• Odaka H, Arai S, Inoue T, Kitaguchi T, Koide T. Genetically-encoded yellow fluorescent cAMP indicator with an expanded dynamic range for dual-color imaging. PLoS One. 2014;9(6):e100252. doi:10.1371/journal.pone.0100252.
   PubMed Web of Science ®Google Scholar