Skip to main content

Advertisement

Log in

Suppression of high-fat-diet-induced obesity in mice by dietary folic acid supplementation is linked to changes in gut microbiota

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

To investigate whether the effects of dietary folic acid supplementation on body weight gain are mediated by gut microbiota in obesity.

Methods

Male C57 BL/6J conventional (CV) and germ-free (GF) mice both aged three to four weeks were fed a high-fat diet (HD), folic acid-deficient HD (FD-HD), folic acid-supplement HD (FS-HD) and a normal-fat diet (ND) for 25 weeks. Faecal microbiota were analyzed by 16S rRNA high-throughput sequencing, and the mRNA expression of genes was determined by the real-time RT-PCR. Short-chain fatty acids (SCFAs) in faeces and plasma were measured using gas chromatography–mass spectrometry.

Results

In CV mice, HD-induced body weight gain was inhibited by FS-HD, accompanied by declined energy intake, smaller white adipocyte size, and less whitening of brown adipose tissue. Meanwhile, the HD-induced disturbance in the expression of fat and energy metabolism-associated genes (Fas, Atgl, Hsl, Ppar-α, adiponectin, resistin, Ucp2, etc.) in epididymal fat was diminished, and the dysbiosis in faecal microbiota was lessened, by FS-HD. However, in GF mice with HD feeding, dietary folic acid supplementation had almost no effect on body weight gain and the expression of fat- and energy-associated genes. Faecal or plasma SCFA concentrations in CV and GF mice were not altered by either FD-HD or FS-HD feeding.

Conclusion

Dietary folic acid supplementation differently affected body weight gain and associated genes’ expression under HD feeding between CV and GF mice, suggesting that gut bacteria might partially share the responsibility for beneficial effects of dietary folate on obesity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C et al (2017) Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 390:2627–2642. https://doi.org/10.1016/S0140-6736(17)32129-3

    Article  Google Scholar 

  2. Engin A (2017) The definition and prevalence of obesity and metabolic syndrome. Adv Exp Med Biol 960:1–17. https://doi.org/10.1007/978-3-319-48382-5_1

    Article  CAS  PubMed  Google Scholar 

  3. Avgerinos KI, Spyrou N, Mantzoros CS, Dalamaga M (2019) Obesity and cancer risk: emerging biological mechanisms and perspectives. Metabolism 92:121–135. https://doi.org/10.1016/j.metabol.2018.11.001

    Article  CAS  PubMed  Google Scholar 

  4. Fanzo J, Davis C (2019) Can diets be healthy, sustainable, and equitable? Curr Obes Rep 8:495–503. https://doi.org/10.1007/s13679-019-00362-0

    Article  PubMed  PubMed Central  Google Scholar 

  5. García OP, Long KZ, Rosado JL (2009) Impact of micronutrient deficiencies on obesity. Nutr Rev 67:559–572. https://doi.org/10.1111/j.1753-4887.2009.00228.x

    Article  PubMed  Google Scholar 

  6. Williams AM, Guo J, Addo OY, Ismaily S, Namaste SML, Oaks BM et al (2019) Intraindividual double burden of overweight or obesity and micronutrient deficiencies or anemia among women of reproductive age in 17 population-based surveys. Am J Clin Nutr 112(Suppl 1):468S-477S. https://doi.org/10.1093/ajcn/nqaa118

    Article  PubMed  Google Scholar 

  7. Thomas-Valdés S, Tostes MDGV, Anunciação PC, da Silva BP, Sant’Ana HMP (2017) Association between vitamin deficiency and metabolic disorders related to obesity. Crit Rev Food Sci Nutr 57:3332–3343. https://doi.org/10.1080/10408398.2015.1117413

    Article  CAS  PubMed  Google Scholar 

  8. Gutema BT, Chuka A, Kondale M, Ayele G, Kote M, Zerdo Z et al (2020) The burden of malnutrition among adults residing in arba minch health and demographic surveillance site (HDSS): a WHO STEPS Survey. J Nutr Metab 2020:6986830. https://doi.org/10.1155/2020/6986830

    Article  PubMed  PubMed Central  Google Scholar 

  9. Oliai Araghi S, Braun KVE, van der Velde N, van Dijk SC, van Schoor NM, Zillikens MC et al (2020) B-vitamins and body composition: integrating observational and experimental evidence from the B-PROOF study. Eur J Nutr 59:1253–1262. https://doi.org/10.1007/s00394-019-01985-8

    Article  CAS  PubMed  Google Scholar 

  10. Zaragoza-Jordana M, Closa-Monasterolo R, Luque V, Ferré N, Grote V, Koletzko B et al (2018) Childhood obesity project group. Micronutrient intake adequacy in children from birth to 8 years. Data from the childhood obesity project. Clin Nutr 37:630–637. https://doi.org/10.1016/j.clnu.2017.02.003

    Article  CAS  PubMed  Google Scholar 

  11. O’Malley EG, Reynolds CME, Cawley S, Woodside JV, Molloy AM, Turner MJ (2018) Folate and vitamin B12 levels in early pregnancy and maternal obesity. Eur J Obstet Gynecol Reprod Biol 231:80–84. https://doi.org/10.1016/j.ejogrb.2018.10.001

    Article  CAS  PubMed  Google Scholar 

  12. Krzizek EC, Brix JM, Herz CT, Kopp HP, Schernthaner GH, Schernthaner G et al (2018) Prevalence of micronutrient deficiency in patients with morbid obesity before bariatric surgery. Obes Surg 28:643–648. https://doi.org/10.1007/s11695-017-2902-4

    Article  PubMed  Google Scholar 

  13. Mlodzik-Czyzewska MA, Malinowska AM, Chmurzynska A (2020) Low folate intake and serum levels are associated with higher body mass index and abdominal fat accumulation: a case control study. Nutr J 19:53. https://doi.org/10.1186/s12937-020-00572-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Li Z, Gueant-Rodriguez RM, Quilliot D, Sirveaux MA, Meyre D, Gueant JL et al (2018) Folate and vitamin B12 status is associated with insulin resistance and metabolic syndrome in morbid obesity. Clin Nutr 37:1700–1706. https://doi.org/10.1016/j.clnu.2017.07.008

    Article  CAS  PubMed  Google Scholar 

  15. Wang G, Hu FB, Mistry KB, Zhang C, Ren F, Huo Y et al (2016) Association between maternal prepregnancy body mass index and plasma folate concentrations with child metabolic health. JAMA Pediatr 170:e160845. https://doi.org/10.1001/jamapediatrics.2016.0845

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang G, DiBari J, Bind E, Steffens AM, Mukherjee J, Azuine RE et al (2019) Association between maternal exposure to lead, maternal folate status, and intergenerational risk of childhood overweight and obesity. JAMA Netw Open 2:e1912343. https://doi.org/10.1001/jamanetworkopen.2019.12343

    Article  PubMed  PubMed Central  Google Scholar 

  17. Xie RH, Liu YJ, Retnakaran R, MacFarlane AJ, Hamilton J, Smith G et al (2016) Maternal folate status and obesity/insulin resistance in the offspring: a systematic review. Int J Obes (Lond) 40:1–9. https://doi.org/10.1038/ijo.2015.189

    Article  CAS  Google Scholar 

  18. Bird JK, Murphy RA, Ciappio ED, McBurney MI (2017) Risk of deficiency in multiple concurrent micronutrients in children and adults in the United States. Nutrients 9:655. https://doi.org/10.3390/nu9070655

    Article  CAS  PubMed Central  Google Scholar 

  19. Titcomb TJ, Tanumihardjo SA (2019) Global concerns with B vitamin statuses: biofortification, fortification, hidden hunger, interactions, and toxicity. Compr Rev Food Sci Food Saf 18:1968–1984. https://doi.org/10.1111/1541-4337.12491

    Article  CAS  PubMed  Google Scholar 

  20. Sheu WH, Chin HM, Lee WJ, Wan CJ, Su HY, Lang HF (2005) Prospective evaluation of folic acid supplementation on plasma homocysteine concentrations during weight reduction: a randomized, double-blinded, placebo-controlled study in obese women. Life Sci 76:2137–2145. https://doi.org/10.1016/j.lfs.2004.12.002

    Article  CAS  PubMed  Google Scholar 

  21. Gargari BP, Aghamohammadi V, Aliasgharzadeh A (2011) Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes. Diabetes Res Clin Pract 94:33–38. https://doi.org/10.1016/j.diabres.2011.07.003

    Article  CAS  PubMed  Google Scholar 

  22. Navarrete-Muñoz EM, Vioque J, Toledo E, Oncina-Canovas A, Martínez-González MÁ, Salas-Salvadó J et al (2021) Dietary folate intake and metabolic syndrome in participants of PREDIMED-Plus study: a cross-sectional study. Eur J Nutr 60:1125–1136. https://doi.org/10.1007/s00394-020-02364-4

    Article  CAS  PubMed  Google Scholar 

  23. Iamopas O, Ratanachu-ek S, Chomtho S (2014) Effect of folic acid supplementation on plasma homocysteine in obese children: a randomized, double-blind, placebo-controlled trial. J Med Assoc Thai 97(Suppl 6):S195-204

    PubMed  Google Scholar 

  24. Li W, Tang R, Ouyang S, Ma F, Liu Z, Wu J (2017) Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity. Nutr Metab (Lond) 14:68. https://doi.org/10.1186/s12986-017-0224-0

    Article  CAS  Google Scholar 

  25. Li W, Tang R, Ma F, Ouyang S, Liu Z, Wu J (2018) Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice. J Nutr Biochem 59:76–83. https://doi.org/10.1016/j.jnutbio.2018.05.010

    Article  CAS  PubMed  Google Scholar 

  26. Buettner R, Bettermann I, Hechtl C, Gäbele E, Hellerbrand C, Schölmerich J et al (2010) Dietary folic acid activates AMPK and improves insulin resistance and hepatic inflammation in dietary rodent models of the metabolic syndrome. Horm Metab Res 42:769–774. https://doi.org/10.1055/s-0030-1263122

    Article  CAS  PubMed  Google Scholar 

  27. LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M (2013) Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol 24:160–168. https://doi.org/10.1016/j.copbio.2012.08.005

    Article  CAS  PubMed  Google Scholar 

  28. LeBlanc JG, Chain F, Martin R, Bermudez-Humaran LG, Courau S, Langella P (2017) Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact 16:79. https://doi.org/10.1186/s12934-017-0691-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pompei A, Cordisco L, Amaretti A, Zanoni S, Matteuzzi D, Rossi M (2007) Folate production by bifidobacteria as a potential probiotic property. Appl Environ Microbiol 73:179–185. https://doi.org/10.1128/AEM.01763-06

    Article  CAS  PubMed  Google Scholar 

  30. Pompei A, Cordisco L, Amaretti A, Zanoni S, Raimondi S, Matteuzzi D, Rossi M (2007) Administration of folate-producing bifidobacteria enhances folate status in Wistar rats. J Nutr 137:2742–2746. https://doi.org/10.1093/jn/137.12.2742

    Article  CAS  PubMed  Google Scholar 

  31. Kok DE, Steegenga WT, McKay JA (2018) Folate and epigenetics: why we should not forget bacterial biosynthesis. Epigenomics 10:1147–1150. https://doi.org/10.2217/epi-2018-0117

    Article  CAS  PubMed  Google Scholar 

  32. Degnan PH, Barry NA, Mok KC, Taga ME, Goodman AL (2014) Human gut microbes use multiple transporters to distinguish vitamin B12 analogs and compete in the gut. Cell Host Microbe 15:47–57. https://doi.org/10.1016/j.chom.2013.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sonnenburg JL, Bäckhed F (2016) Diet-microbiota interactions as moderators of human metabolism. Nature 535:56–64. https://doi.org/10.1038/nature18846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Heiss CN, Olofsson LE (2018) Gut microbiota-dependent modulation of energy metabolism. J Innate Immun 10:163–171. https://doi.org/10.1159/000481519

    Article  CAS  PubMed  Google Scholar 

  35. Wang R, Fan C, Fan X, Zhao Y, Wang Y, Li P et al (2020) A fast and accurate way to determine short chain fatty acids in human serum by GC–MS and their distribution in children with digestive diseases. Chromatographia 83:273–286. https://doi.org/10.1007/s10337-019-03831-9

    Article  CAS  Google Scholar 

  36. van Bennekum AM, Kako Y, Weinstock PH, Harrison EH, Deckelbaum RJ, Goldberg IJ, Blaner WS (1999) Lipoprotein lipase expression level influences tissue clearance of chylomicron retinyl ester. J Lipid Res 40:565–574

    Article  PubMed  Google Scholar 

  37. Yao H, Fan C, Lu Y, Fan X, Xia L, Li P et al (2020) Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice. Genes Nutr 15:12. https://doi.org/10.1186/s12263-020-00671-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li P, Tang T, Chang X, Fan X, Chen X, Wang R et al (2019) Abnormality in maternal dietary calcium intake during pregnancy and lactation promotes body weight gain by affecting the gut microbiota in mouse offspring. Mol Nutr Food Res 63:e1800399. https://doi.org/10.1002/mnfr.201800399

    Article  CAS  PubMed  Google Scholar 

  39. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12:R60. https://doi.org/10.1186/gb-2011-12-6-r60

    Article  PubMed  PubMed Central  Google Scholar 

  40. Fan X, Yao H, Liu X, Shi Q, Lv L, Li P et al (2020) High-fat diet alters the expression of reference genes in male mice. Front Nutr 7:589771. https://doi.org/10.3389/fnut.2020.589771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Naderi N, House JD (2018) Recent developments in folate nutrition. Adv Food Nutr Res 83:195–213. https://doi.org/10.1016/bs.afnr.2017.12.006

    Article  PubMed  Google Scholar 

  42. Crider KS, Yang TP, Berry RJ, Bailey LB (2012) Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr 3:21–38. https://doi.org/10.3945/an.111.000992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Xin FZ, Zhao ZH, Zhang RN, Pan Q, Gong ZZ, Sun C, Fan JG (2020) Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPARalpha. World J Gastroenterol 26:2203–2220. https://doi.org/10.3748/wjg.v26.i18.2203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chen H, Zhang L, Li X, Li X, Sun G, Yuan X et al (2013) Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes. J Steroid Biochem Mol Biol 138:445–454. https://doi.org/10.1016/j.jsbmb.2013.08.013

    Article  CAS  PubMed  Google Scholar 

  45. O’Neill HM, Holloway GP, Steinberg GR (2013) AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity. Mol Cell Endocrinol 366:135–151. https://doi.org/10.1016/j.mce.2012.06.019

    Article  CAS  PubMed  Google Scholar 

  46. Bazhan NM, Baklanov AV, Piskunova JV, Kazantseva AJ, Makarova EN (2017) Expression of genes involved in carbohydrate-lipid metabolism in muscle and fat tissues in the initial stage of adult-age obesity in fed and fasted mice. Physiol Rep. https://doi.org/10.14814/phy2.13445

    Article  PubMed  PubMed Central  Google Scholar 

  47. Yasrebi A, Hsieh A, Mamounis KJ, Krumm EA, Yang JA, Magby J, Hu P, Roepke TA (2016) Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17beta-estradiol. Mol Cell Endocrinol 422:42–56. https://doi.org/10.1016/j.mce.2015.11.007

    Article  CAS  PubMed  Google Scholar 

  48. Bird JK, Ronnenberg AG, Choi SW, Du F, Mason JB, Liu Z (2015) Obesity is associated with increased red blood cell folate despite lower dietary intakes and serum concentrations. J Nutr 145(1):79–86. https://doi.org/10.3945/jn.114.199117

    Article  CAS  PubMed  Google Scholar 

  49. Tinker SC, Hamner HC, Berry RJ, Bailey LB, Pfeiffer CM (2012) Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States? Birth Defects Res A Clin Mol Teratol 94:749–755. https://doi.org/10.1002/bdra.23024

    Article  CAS  PubMed  Google Scholar 

  50. Kose S, Sozlu S, Bolukbasi H, Unsal N, Gezmen-Karadag M (2020) Obesity is associated with folate metabolism. Int J Vitam Nutr Res 90:353–364. https://doi.org/10.1024/0300-9831/a000602

    Article  CAS  PubMed  Google Scholar 

  51. Wostmann BS (2020) Germfree and gnotobiotic animal models: background and applications. CRC Press (ISBN, 0429610890, 9780429610899)

    Book  Google Scholar 

  52. Rabot S, Membrez M, Bruneau A, Gérard P, Harach T, Moser M et al (2010) Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J 24:4948–4959. https://doi.org/10.1096/fj.10-164921

    Article  CAS  PubMed  Google Scholar 

  53. Fleissner CK, Huebel N, Abd El-Bary MM, Loh G, Klaus S, Blaut M (2010) Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr 104:919–929. https://doi.org/10.1017/S0007114510001303

    Article  CAS  PubMed  Google Scholar 

  54. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104:979–984. https://doi.org/10.1073/pnas.0605374104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dabke K, Hendrick G, Devkota S (2019) The gut microbiome and metabolic syndrome. J Clin Invest 129:4050–4057. https://doi.org/10.1172/JCI129194

    Article  PubMed  PubMed Central  Google Scholar 

  56. Zhuang P, Zhang Y, Shou Q, Li H, Zhu Y, He L et al (2020) Eicosapentaenoic and docosahexaenoic acids differentially alter gut microbiome and reverse high-fat diet-induced insulin resistance. Mol Nutr Food Res 64:e1900946. https://doi.org/10.1002/mnfr.201900946

    Article  CAS  PubMed  Google Scholar 

  57. Hou D, Zhao Q, Yousaf L, Xue Y, Shen Q (2020) Beneficial effects of mung bean seed coat on the prevention of high-fat diet-induced obesity and the modulation of gut microbiota in mice. Eur J Nutr 60:2029–2045. https://doi.org/10.1007/s00394-020-02395-x

    Article  CAS  PubMed  Google Scholar 

  58. Guo J, Han X, Zhan J, You Y, Huang W (2018) Vanillin alleviates high fat diet-induced obesity and improves the gut microbiota composition. Front Microbiol 9:2733. https://doi.org/10.3389/fmicb.2018.02733

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wang P, Gao J, Ke W, Wang J, Li D, Liu R et al (2020) Resveratrol reduces obesity in high-fat diet-fed mice via modulating the composition and metabolic function of the gut microbiota. Free Radic Biol Med 156:83–98. https://doi.org/10.1016/j.freeradbiomed.2020.04.013

    Article  CAS  PubMed  Google Scholar 

  60. Zhao L, Zhang Q, Ma W, Tian F, Shen H, Zhou M (2017) A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food Funct 8:4644–4656. https://doi.org/10.1039/c7fo01383c

    Article  CAS  PubMed  Google Scholar 

  61. Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C et al (2013) Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut 62:1787–1794. https://doi.org/10.1136/gutjnl-2012-303816

    Article  CAS  PubMed  Google Scholar 

  62. Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C et al (2012) Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS ONE. https://doi.org/10.1371/journal.pone.0042529

    Article  PubMed  PubMed Central  Google Scholar 

  63. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O et al (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58:1091–1103. https://doi.org/10.1136/gut.2008.165886

    Article  CAS  PubMed  Google Scholar 

  64. Lam YY, Ha CW, Campbell CR, Mitchell AJ, Dinudom A, Oscarsson J et al (2012) Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS ONE. https://doi.org/10.1371/journal.pone.0034233

    Article  PubMed  PubMed Central  Google Scholar 

  65. Duca FA, Sakar Y, Lepage P, Devime F, Langelier B, Doré J, Covasa M (2014) Replication of obesity and associated signaling pathways through transfer of microbiota from obese-prone rats. Diabetes 63:1624–1636. https://doi.org/10.2337/db13-1526

    Article  CAS  PubMed  Google Scholar 

  66. Beaumont M, Andriamihaja M, Lan A, Khodorova N, Audebert M, Blouin JM et al (2016) Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: the adaptive response. Free Radic Biol Med 93:155–164. https://doi.org/10.1016/j.freeradbiomed.2016.01.028

    Article  CAS  PubMed  Google Scholar 

  67. Sun WZ, Augusto LA, Zhao LP, Caroff M (2015) Desulfovibrio desulfuricans isolates from the gut of a single individual: structural and biological lipid a characterization. FEBS Lett 589:165–171. https://doi.org/10.1016/j.febslet.2014.11.042

    Article  CAS  Google Scholar 

  68. Chambers ES, Preston T, Frost G, Morrison DJ (2018) Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr Nutr Rep 7:198–206. https://doi.org/10.1007/s13668-018-0248-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kumari M, Kozyrskyj AL (2017) Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation. Obes Rev 18:18–31. https://doi.org/10.1111/obr.12484

    Article  CAS  PubMed  Google Scholar 

  70. Natividad JM, Lamas B, Pham HP, Michel ML, Rainteau D, Bridonneau C et al (2018) Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice. Nat Commun. https://doi.org/10.1038/s41467-018-05249-7

    Article  PubMed  PubMed Central  Google Scholar 

  71. Morowitz MJ, Carlisle EM, Alverdy JC (2011) Contributions of intestinal bacteria to nutrition and metabolism in the critically ill. Surg Clin North Am. https://doi.org/10.1016/j.suc.2011.05.001

    Article  PubMed  PubMed Central  Google Scholar 

  72. Magnusdottir S, Ravcheev D, de Crecy-Lagard V, Thiele I (2015) Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. https://doi.org/10.3389/fgene.2015.00148

    Article  PubMed  PubMed Central  Google Scholar 

  73. Engevik MA, Morra CN, Röth D, Engevik K, Spinler JK, Devaraj S, Crawford SE, Estes MK, Kalkum M, Versalovic J (2019) Microbial metabolic capacity for intestinal folate production and modulation of host folate receptors. Front Microbiol. https://doi.org/10.3389/fmicb.2019.02305

    Article  PubMed  PubMed Central  Google Scholar 

  74. Asrar FM, O’Connor DL (2005) Bacterially synthesized folate and supplemental folic acid are absorbed across the large intestine of piglets. J Nutr Biochem 16:587–593. https://doi.org/10.1016/j.jnutbio.2005.02.006

    Article  CAS  PubMed  Google Scholar 

  75. Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I (2015) Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients 7:2839–2849. https://doi.org/10.3390/nu7042839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lu Y, Fan C, Li P, Lu Y, Chang X, Qi K (2016) Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating G protein-coupled receptors and gut microbiota. Sci Rep 6:37589. https://doi.org/10.1038/srep37589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, Kobayashi M, Hirasawa A, Tsujimoto G (2011) Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci USA 108:8030–8035. https://doi.org/10.1073/pnas.1016088108

    Article  PubMed  PubMed Central  Google Scholar 

  78. LeBlanc JG, Chain F, Martín R, Bermúdez-Humarán LG, Courau S, Langella P (2017) Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact. https://doi.org/10.1186/s12934-017-0691-z

    Article  PubMed  PubMed Central  Google Scholar 

  79. Choi SI, Son JH, Kim N, Kim YS, Nam RH, Park JH, Song CH, Yu JE, Lee DH, Yoon K, Min H, Kim YR, Seok YJ (2021) Changes in cecal microbiota and short-chain fatty acid during lifespan of the rat. J Neurogastroenterol Motil 27:134–146. https://doi.org/10.5056/jnm20148

    Article  PubMed  PubMed Central  Google Scholar 

  80. Hu S, Xu Y, Gao X, Li S, Jiang W, Liu Y, Su L, Yang H (2019) Long-chain bases from sea cucumber alleviate obesity by modulating gut microbiota. Mar Drugs. https://doi.org/10.3390/md17080455

    Article  PubMed  PubMed Central  Google Scholar 

  81. Sivaprakasam S, Prasad PD, Singh N (2016) Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis. Pharmacol Ther 164:144–151. https://doi.org/10.1016/j.pharmthera.2016.04.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Layden BT, Angueira AR, Brodsky M, Durai V, Lowe WL Jr (2013) Short chain fatty acids and their receptors: new metabolic targets. Transl Res 161:131–140. https://doi.org/10.1016/j.trsl.2012.10.007

    Article  CAS  PubMed  Google Scholar 

  83. Høverstad T, Midtvedt T (1986) Short-chain fatty acids in germfree mice and rats. J Nutr 116:1772–1776. https://doi.org/10.1093/jn/116.9.1772

    Article  PubMed  Google Scholar 

  84. Huang Z, Zhang M, Plec AA, Estill SJ, Cai L, Repa JJ, McKnight SL, Tu BP (2018) ACSS2 promotes systemic fat storage and utilization through selective regulation of genes involved in lipid metabolism. Proc Natl Acad Sci U S A 115:E9499–E9506. https://doi.org/10.1073/pnas.1806635115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yao H, Fan C, Fan X, Lu Y, Wang Y, Wang R, Tang T, Qi K (2020) Effects of gut microbiota on leptin expression and body weight are lessened by high-fat diet in mice. Br J Nutr 124:396–406. https://doi.org/10.1017/S0007114520001117

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (to K.Q. No.81670775), and the Research Funds of Profession Quota Budget from Beijing Municipal Science and Technology Commission (2020-bjsekyjs to K.Q.).

Author information

Authors and Affiliations

Authors

Contributions

SC and KQ contributed to the study conception and design. SC, XF and TT performed the experiments and collected the data. MY and RW performed fecal microbiota analysis. PL and XZ instructed the statistical analysis. The manuscript was written by SC and KQ. All authors commented on previous versions of the manuscript, and approved the final manuscript.

Corresponding author

Correspondence to Kemin Qi.

Ethics declarations

Conflict of interest

All authors declare that they have no commercial conflict of interest.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Yang, M., Wang, R. et al. Suppression of high-fat-diet-induced obesity in mice by dietary folic acid supplementation is linked to changes in gut microbiota. Eur J Nutr 61, 2015–2031 (2022). https://doi.org/10.1007/s00394-021-02769-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-021-02769-9

Keywords

Navigation