Skip to main content
Log in

Oral administration of Flavonifractor plautii attenuates inflammatory responses in obese adipose tissue

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Adipose tissue inflammation enhances the symptoms of metabolic syndrome. Flavonifractor plautii, a bacterium present in human feces, has been reported to participate in the metabolism of catechin in the gut. The precise function of F. plautii remains unclear. We assessed the immunoregulatory function of F. plautii both in vitro and in vivo. In vitro, we showed that both viable and heat-killed F. plautii attenuated TNF-α transcript accumulation in lipopolysaccharide-stimulated RAW 264.7 cells. For the in vivo experiment, male C57BL/6 were placed on a high-fat diet (HFD) for 11 weeks. During the final two weeks on the HFD, the animals were administered with F. plautii by once-daily oral gavage. The oral administration of F. plautii attenuated the increase in TNF-α transcription otherwise seen in the epididymal adipose tissue of HFD-fed obese mice (HFD + F. plautii). The composition of the microbial population (at the genus level) in the cecal contents of the HFD + F. plautii mice was altered considerably. In particular, the level of Sphingobium was decreased significantly, and that of Lachnospiraceae was increased significantly, in the HFD + F. plautii group. Obesity is closely associated with the development of inflammation in adipose tissue. F. plautii may be involved in inhibition of TNF-α expression in inflammatory environments. Our results demonstrated that F. plautii may be useful for alleviating the inflammatory responses of adipose tissue.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Heimler D, Romani A, Ieri F (2017) Plant polyphenol content, soil fertilization and agricultural management: a review. Eur Food Res Technol 243(7):1107–1115. https://doi.org/10.1007/s00217-016-2826-6

    Article  CAS  Google Scholar 

  2. Chew B, Mathison B, Kimble L, McKay D, Kaspar K, Khoo C, Chen CO, Blumberg J (2018) Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial. Eur J Nutr. https://doi.org/10.1007/s00394-018-1643-z

    Article  PubMed  PubMed Central  Google Scholar 

  3. Vernarelli JA, Lambert JD (2017) Flavonoid intake is inversely associated with obesity and C-reactive protein, a marker for inflammation. US adults Nutr Diabetes 7(5):e276. https://doi.org/10.1038/nutd.2017.22

    Article  CAS  PubMed  Google Scholar 

  4. Linglin Fu JS, Wang C, Shujie Fu, Wang Y (2017) Bifidobacterium infantis potentially alleviates shrimp tropomyosin-induced allergy by tolerogenic dendritic cell-dependent induction of regulatory T cells and alterations in gut microbiota. Front Immunol 8:1536. https://doi.org/10.3389/fimmu.2017.01536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Janssens PL, Hursel R, Westerterp-Plantenga MS (2016) Nutraceuticals for body-weight management: the role of green tea catechins. Physiol Behav 162:83–87. https://doi.org/10.1016/j.physbeh.2016.01.044

    Article  CAS  PubMed  Google Scholar 

  6. Cardozo Junior EL, Morand C (2016) Interest of mate ( Ilex paraguariensis A. St.-Hil.) as a new natural functional food to preserve human cardiovascular health: a review. J Funct Foods 21:440–454. https://doi.org/10.1016/j.jff.2015.12.010

    Article  CAS  Google Scholar 

  7. Manach CWG, Morand C, Scalbert A, Rémésy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81(1):S230S–S242

    Article  Google Scholar 

  8. Janssens PL, Penders J, Hursel R, Budding AE, Savelkoul PH, Westerterp-Plantenga MS (2016) Long-term green tea supplementation does not change the human gut microbiota. PLoS ONE 11(4):e0153134. https://doi.org/10.1371/journal.pone.0153134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ozdal T, Sela DA, Xiao J, Boyacioglu D, Chen F, Capanoglu E (2016) The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients 8(2):78. https://doi.org/10.3390/nu8020078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S, Taniguchi T, Morita H, Hattori M, Honda K (2013) Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500(7461):232–236. https://doi.org/10.1038/nature12331

    Article  CAS  PubMed  Google Scholar 

  11. Carlier JP, Bedora-Faure M, K'Ouas G, Alauzet C, Mory F (2010) Proposal to unify Clostridium orbiscindens Winter et al. 1991 and Eubacterium plautii (Seguin 1928) Hofstad and Aasjord 1982, with description of Flavonifractor plautii gen. nov., comb. nov., and reassignment of Bacteroides capillosus to Pseudoflavonifractor capillosus gen. nov., comb. nov. Int J Syst Evol Microbiol 60(3):585–590. https://doi.org/10.1099/ijs.0.016725-0

    Article  CAS  PubMed  Google Scholar 

  12. Ogita T, Yamamoto Y, Mikami A, Shigemori S, Sato T, Shimosato T (2020) Oral Administration of flavonifractor plautii strongly suppresses Th2 immune responses in mice. Front Immunol 11:379. https://doi.org/10.3389/fimmu.2020.00379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444(7121):860–867

    Article  CAS  PubMed  Google Scholar 

  14. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112(12):1821–1830. https://doi.org/10.1172/jci200319451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Takagi T, Naito Y, Inoue R, Kashiwagi S, Uchiyama K, Mizushima K, Tsuchiya S, Dohi O, Yoshida N, Kamada K, Ishikawa T, Handa O, Konishi H, Okuda K, Tsujimoto Y, Ohnogi H, Itoh Y (2019) Differences in gut microbiota associated with age, sex, and stool consistency in healthy Japanese subjects. J Gastroenterol 54(1):53–63. https://doi.org/10.1007/s00535-018-1488-5

    Article  PubMed  Google Scholar 

  16. Chen X, Xia C, Li Q, Jin L, Zheng L, Wu Z (2018) Comparisons between bacterial communities in mucosa in patients with gastric antrum ulcer and a duodenal ulcer. Front Cell Infect Microbiol. https://doi.org/10.3389/fcimb.2018.00126

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chakraborty S, Galla S, Cheng X, Yeo JY, Mell B, Singh V, Yeoh B, Saha P, Mathew AV, Vijay-Kumar M, Joe B (2018) Salt-responsive metabolite, beta-hydroxybutyrate, attenuates hypertension. Cell Rep 25(3):677–689. https://doi.org/10.1016/j.celrep.2018.09.058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Faith DP (1992) Conservation evaluation and phylogenetic diversity. Biol Conserv 61(1):1–10

    Article  Google Scholar 

  19. Faith DP (1994) Genetic diversity and taxonomic priorities for conservation. Biol Conserv 68(1):69–74

    Article  Google Scholar 

  20. Lozupone C, Knight R (2005) UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol 71(12):8228–8235. https://doi.org/10.1128/AEM.71.12.8228-8235.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nicola Segata JI, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12:R60

    Article  PubMed  PubMed Central  Google Scholar 

  22. De Simone V, Franze E, Ronchetti G, Colantoni A, Fantini MC, Di Fusco D, Sica GS, Sileri P, MacDonald TT, Pallone F, Monteleone G, Stolfi C (2015) Th17-type cytokines, IL-6 and TNF-alpha synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene 34(27):3493–3503. https://doi.org/10.1038/onc.2014.286

    Article  CAS  PubMed  Google Scholar 

  23. Katzmarzyk PT, Barreira TV, Broyles ST, Champagne CM, Chaput JP, Fogelholm M, Hu G, Johnson WD, Kuriyan R, Kurpad A, Lambert EV, Maher C, Maia J, Matsudo V, Olds T, Onywera V, Sarmiento OL, Standage M, Tremblay MS, Tudor-Locke C, Zhao P, Church TS, Group IR (2015) Relationship between lifestyle behaviors and obesity in children ages 9–11: Results from a 12-country study. Obesity (Silver Spring) 23(8):1696–1702. https://doi.org/10.1002/oby.21152

    Article  Google Scholar 

  24. Alcala M, Calderon-Dominguez M, Bustos E, Ramos P, Casals N, Serra D, Viana M, Herrero L (2017) Increased inflammation, oxidative stress and mitochondrial respiration in brown adipose tissue from obese mice. Sci Rep 7(1):16082. https://doi.org/10.1038/s41598-017-16463-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Appari M, Channon KM, McNeill E (2018) Metabolic regulation of adipose tissue macrophage function in obesity and diabetes. Antioxid Redox Signal 29(3):297–312. https://doi.org/10.1089/ars.2017.7060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Patterson E, Ryan PM, Cryan JF, Dinan TG, Ross RP, Fitzgerald GF, Stanton C (2016) Gut microbiota, obesity and diabetes. Postgrad Med J 92(1087):286–300. https://doi.org/10.1136/postgradmedj-2015-133285

    Article  CAS  PubMed  Google Scholar 

  27. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1031. https://doi.org/10.1038/nature05414

    Article  PubMed  Google Scholar 

  28. Madani Z, Louchami K, Sener A, Malaisse WJ, Ait Yahia D (2012) Dietary sardine protein lowers insulin resistance, leptin and TNF-alpha and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome. Int J Mol Med 29(2):311–318. https://doi.org/10.3892/ijmm.2011.836

    Article  CAS  PubMed  Google Scholar 

  29. Zhang Z, Zhou Z, Li Y, Zhou L, Ding Q, Xu L (2016) Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice. Sci Rep 6:36083. https://doi.org/10.1038/srep36083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yazdani B, Shidfar F, Salehi E, Baghbani-arani F, Razmpoosh E, Asemi Z, Cheshmazar E, Zarrati M (2018) Probiotic plus low-calorie diet increase gene expression of Toll-like receptor 2 and FOXP3 in overweight and obese participants. J Funct Foods 43:180–185. https://doi.org/10.1016/j.jff.2018.02.013

    Article  CAS  Google Scholar 

  31. Helsley RN, Sui Y, Park SH, Liu Z, Lee RG, Zhu B, Kern PA, Zhou C (2016) Targeting IkappaB kinase beta in adipocyte lineage cells for treatment of obesity and metabolic dysfunctions. Stem Cells 34(7):1883–1895. https://doi.org/10.1002/stem.2358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cipolletta D, Cohen P, Spiegelman BM, Benoist C, Mathis D (2015) Appearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: age, diet, and PPARgamma effects. Proc Natl Acad Sci US A 112(2):482–487. https://doi.org/10.1073/pnas.1423486112

    Article  CAS  Google Scholar 

  33. Berger FK, Schwab N, Glanemann M, Bohle RM, Gartner B, Groesdonk HV (2018) Flavonifractor (Eubacterium) plautii bloodstream infection following acute cholecystitis. IDCases 14:e00461. https://doi.org/10.1016/j.idcr.2018.e00461

    Article  PubMed  PubMed Central  Google Scholar 

  34. Li X, Zeng F, Huang Y, Liu B (2019) The positive effects of Grifola frondosa heteropolysaccharide on NAFLD and regulation of the gut microbiota. Int J Mol Sci. https://doi.org/10.3390/ijms20215302

    Article  PubMed  PubMed Central  Google Scholar 

  35. Luna RA, Oezguen N, Balderas M, Venkatachalam A, Runge JK, Versalovic J, Veenstra-VanderWeele J, Anderson GM, Savidge T, Williams KC (2017) Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder. Cell Mol Gastroenterol Hepatol 3(2):218–230. https://doi.org/10.1016/j.jcmgh.2016.11.008

    Article  PubMed  Google Scholar 

  36. Gupta A, Dhakan DB, Maji A, Saxena R, Mahajan PKV, Pulikkan S, Kurian J, Gomez AM, Scaria J, Amato KR, Sharma AK, Sharma VK (2019) Association of Flavonifractor plautii, a flavonoid-degrading bacterium, with the gut microbiome of Colorectal Cancer Patients in India. Systems. https://doi.org/10.1128/mSystems.00438-19

    Article  Google Scholar 

  37. Song YF, Pei LX, Chen L, Geng H, Yuan MQ, Xu WL, Wu J, Zhou JY, Sun JH (2020) Electroacupuncture relieves irritable bowel syndrome by regulating IL-18 and gut microbial dysbiosis in a trinitrobenzene sulfonic acid-induced post-inflammatory animal model. Am J Chin Med 48(1):77–90. https://doi.org/10.1142/S0192415X20500044

    Article  CAS  PubMed  Google Scholar 

  38. Wingender G, Stepniak D, Krebs P, Lin L, McBride S, Wei B, Braun J, Mazmanian SK, Kronenberg M (2012) Intestinal microbes affect phenotypes and functions of invariant natural killer T cells in mice. Gastroenterology 143(2):418–428. https://doi.org/10.1053/j.gastro.2012.04.017

    Article  CAS  PubMed  Google Scholar 

  39. Watanabe M, Kaku N, Ueki K, Ueki A (2016) Falcatimonas natans gen nov, sp nov, a strictly anaerobic, amino-acid-decomposing bacterium isolated from a methanogenic reactor of cattle waste. Int J Syst Evol Microbiol 66(11):4639–4644. https://doi.org/10.1099/ijsem.0.001403

    Article  CAS  PubMed  Google Scholar 

  40. Onrust L, Ducatelle R, Van Driessche K, De Maesschalck C, Vermeulen K, Haesebrouck F, Eeckhaut V, Van Immerseel F (2015) Steering endogenous butyrate production in the intestinal tract of broilers as a tool to improve gut health. Front Vet Sci 2:75. https://doi.org/10.3389/fvets.2015.00075

    Article  PubMed  PubMed Central  Google Scholar 

  41. Bianchi F, Larsen N, de Mello TT, Adorno MAT, Kot W, Saad SMI, Jespersen L, Sivieri K (2018) Modulation of gut microbiota from obese individuals by in vitro fermentation of citrus pectin in combination with Bifidobacterium longum BB-46. Appl Microbiol Biotechnol 102(20):8827–8840. https://doi.org/10.1007/s00253-018-9234-8

    Article  CAS  PubMed  Google Scholar 

  42. Kasai C, Sugimoto K, Moritani I, Tanaka J, Oya Y, Inoue H, Tameda M, Shiraki K, Ito M, Takei Y, Takase K (2015) Comparison of the gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing. BMC Gastroenterol 15:100. https://doi.org/10.1186/s12876-015-0330-2

    Article  PubMed  PubMed Central  Google Scholar 

  43. Borgo F, Garbossa S, Riva A, Severgnini M, Luigiano C, Benetti A, Pontiroli AE, Morace G, Borghi E (2018) Body mass index and sex affect diverse microbial niches within the gut. Front Microbiol 9:213. https://doi.org/10.3389/fmicb.2018.00213

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by JSPS KAKENHI Grant Number 17K15268 to TO. We also thank The Research Center for Support of Advanced Science, Shinshu University, for use of their facilities.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takeshi Shimosato.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experimental procedures were carried out in accordance with the Regulations for Animal Experimentation of Shinshu University. All experimental procedures were reviewed by the Committee for Animal Experiments of Shinshu University and found to be compliant with national regulations and guidelines, as specified by Law No. 105 and Notification No. 6. The animal protocol was approved by the Committee for Animal Experiments of Shinshu University as Approval No. 300054.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mikami, A., Ogita, T., Namai, F. et al. Oral administration of Flavonifractor plautii attenuates inflammatory responses in obese adipose tissue. Mol Biol Rep 47, 6717–6725 (2020). https://doi.org/10.1007/s11033-020-05727-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05727-6

Keywords

Navigation