Advertisement

Gut microbiota is associated with adiposity markers and probiotics may impact specific genera

  • Aline Corado Gomes
  • Christian Hoffmann
  • João Felipe MotaEmail author
Original Contribution

Abstract

Purpose

It has been suggested that restoring gut microbiota alterations with probiotics represents a potential clinical target for the treatment of gut microbiota-related diseases, such as obesity. Here, we apply 16S rDNA microbiota profiling to establish which bacteria in the human gut are associated with obesity and cardiometabolic risk factors, and to evaluate whether probiotic supplementation modulates gut microbiota.

Methods

We evaluated the effects of a probiotic mixture (2 × 1010 CFU/day of Lactobacillus acidophilus LA-14, Lactobacillus casei LC-11, Lactococcus lactis LL-23, Bifidobacterium bifidum BB-06, and Bifidobacterium lactis BL-4) in 32 overweight or obese women in a double-blind, randomized, placebo-controlled study. Using 16S rDNA sequencing, we characterized fecal samples and investigated the relationships between microbiome data and diet, body composition, antioxidant enzymes, and inflammatory profile. In addition, we characterized the degree of variation among fecal communities after the intervention.

Results

BMI, weight, fat mass, lean mass, conicity index, protein intake, monounsaturated fat intake, glycated hemoglobin, TNF-α, and IL6/IL10 were significantly correlated with microbiome composition. The candidate division TM7 was strongly associated with all adiposity markers and Clostridiaceae associated negatively with TNF-α. The family Clostridiaceae increased and TM7 tended to decrease after the probiotic mixture supplementation. Subjects were clustered according to body composition, and a higher proportion of TM7 was observed in those with higher adiposity.

Conclusions

Ecosystem-wide analysis of probiotic use effects on the gut microbiota revealed a genera specific influence, and one of which (TM7) represents a promising novel target for obesity treatment.

Trial registration number

U1111-1137-4566.

Keywords

Obesity Gut microbiota Body composition Probiotics 

Abbreviations

BIC

Bayesian information criterion

CAT

Catalase

CONTROL

Placebo group

GPx

Glutathione peroxidase

LAP

Lipid accumulation product

LPS

Lipopolysaccharide

MDA

Malondialdehyde

OTU

Operational taxonomic unit

PROB

Probiotic mix group

SOD

Superoxide dismutase

Notes

Acknowledgements

The authors wish to thank Dr. Ravila Graziany, Machado de Souza, and Tatyanne Leticia Nogueira Gomes for patient recruitment. The authors thank Dr. Simone Gonçalves da Fonseca for sharing her lab’s structure and Dr. Carla M. Prado for English language review. This work was funded by Fundação de Amparo à Pesquisa do Estado de Goiás—FAPEG (Grant number 201310267001083) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (23038.014292/2018-73).

Funding

This work was funded by Fundação de Amparo à Pesquisa do Estado de Goiás—FAPEG (Grant number 201310267001083) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (23038.014292/2018-73).

Compliance with ethical standards

Conflict of interest

None declared.

Consent for publication

All authors read and approved the final manuscript.

Supplementary material

394_2019_2034_MOESM1_ESM.docx (60 kb)
Supplementary material 1 (DOCX 60 kb)

References

  1. 1.
    Parséus A, Sommer N, Sommer F, Caesar R, Molinaro A, Ståhlman M et al (2016) Microbiota-induced obesity requires farnesoid X receptor. Gut 66:1–9.  https://doi.org/10.1136/gutjnl-2015-310283 Google Scholar
  2. 2.
    Tremaroli V, Bäckhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489:242–249.  https://doi.org/10.1038/nature11552 CrossRefGoogle Scholar
  3. 3.
    Qin J, Li R, Raes J, Arumugam M, Arumugam M, Burgdorf KS, Manichanh C et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65.  https://doi.org/10.1038/nature08821 CrossRefGoogle Scholar
  4. 4.
    Human Microbiome Project Consortium (2012) Structure, function and diversity of the health human microbiome. Nature 486:207–214.  https://doi.org/10.1038/nature11234 CrossRefGoogle Scholar
  5. 5.
    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI et al (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031.  https://doi.org/10.1038/nature05414 CrossRefGoogle Scholar
  6. 6.
    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM et al (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57:1470–1481.  https://doi.org/10.2337/db07-1403 CrossRefGoogle Scholar
  7. 7.
    Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A et al (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101:15718–15723.  https://doi.org/10.1073/pnas.0407076101 CrossRefGoogle Scholar
  8. 8.
    Cammarota G, Ianiro G, Bibbò S, Gasbarrini A (2014) Gut microbiota modulation: probiotics, antibiotics or fecal microbiota transplantation? Intern Emerg Med 9:365–373.  https://doi.org/10.1007/s11739-014-1069-4 CrossRefGoogle Scholar
  9. 9.
    FAO/WHO (2002) Guidelines for the evaluation of probiotics in food: report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in food. WHO/FAO, LondonGoogle Scholar
  10. 10.
    Larsen N, Vogensen FK, Gøbel R, Michaelsen KF, Abu Al-Soud W, Sørensen SJ et al (2011) Predominant genera of fecal microbiota in children with atopic dermatitis are not altered by intake of probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp lactis Bi-07. FEMS Microbiol Ecol 75:482–496.  https://doi.org/10.1111/j.1574-6941.2010.01024 CrossRefGoogle Scholar
  11. 11.
    Lahtinen SJ, Forssten S, Aakko J, Granlund L, Rautonen N, Salminen S et al (2012) Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM® modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly. Age 34:133–143.  https://doi.org/10.1007/s11357-011-9208-6 CrossRefGoogle Scholar
  12. 12.
    West NP, Pyne DB, Cripps AW, Christophersen CT, Conlon MA, Fricker PA et al (2012) Gut Balance, a synbiotic supplement, increases fecal Lactobacillus paracasei but has little effect on immunity in healthy physically active individuals. Gut Microbes 3:221–227.  https://doi.org/10.4161/gmic.19579 CrossRefGoogle Scholar
  13. 13.
    Roos S, Dicksved J, Tarasco V, Locatelli E, Ricceri F, Grandin U et al (2013) 454 pyrosequencing analysis on faecal samples from a randomized DBPC trial of colicky infants treated with Lactobacillus reuteri DSM 17938. PLoS One 8:e56710.  https://doi.org/10.1371/journal.pone.0056710 CrossRefGoogle Scholar
  14. 14.
    Björklund M, Ouwehand AC, Forssten SD, Nikkilä J, Tiihonen K, Rautonen N et al (2012) Gut microbiota of healthy elderly NSAID users is selectively modified with the administration of Lactobacillus acidophilus NCFM and lactitol. Age 4:987–999.  https://doi.org/10.1007/s11357-011-9294-5 CrossRefGoogle Scholar
  15. 15.
    Larsen N, Vogensen FK, Gøbel RJ, Michaelsen KF, Forssten SD, Lahtinen SJ et al (2013) Effect of Lactobacillus salivarius Ls-33 on fecal microbiota in obese adolescents. Clin Nutr 32:935–940.  https://doi.org/10.1016/j.clnu.2013.02.007 CrossRefGoogle Scholar
  16. 16.
    Zhang H, Sun J, Liu X, Michaelsen KF, Forssten SD, Lahtinen SJ et al (2013) Lactobacillus paracasei subsp paracasei LC01 positively modulates intestinal microflora in healthy young adults. J Microbiol 51:777–782.  https://doi.org/10.1007/s12275-013-3279-2 CrossRefGoogle Scholar
  17. 17.
    Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, Puri P, Sterling RK et al (2014) Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Aliment Pharmacol Ther 39:1113–1125.  https://doi.org/10.1111/apt.12695 CrossRefGoogle Scholar
  18. 18.
    Gomes AC, De Sousa RGM, Botelho PB, Gomes TL, Prada PO, Mota JF (2017) The additional effects of a probiotic mix on abdominal adiposity and antioxidant Status: a double-blind, randomized trial. Obesity (Silver Spring, Md.) 25:30–38.  https://doi.org/10.1002/oby.21671 CrossRefGoogle Scholar
  19. 19.
    La Rosa PS, Brooks JP, Deych E, Boone EL, Edwards DJ, Wang Q et al (2012) Hypothesis testing and power calculations for taxonomic-based human microbiome data. PLoS One 7(1):e52078.  https://doi.org/10.1371/journal.pone.0052078 CrossRefGoogle Scholar
  20. 20.
    Kelly BJ, Gross R, Bittinger K, Sherrill-Mix S, Lewis JD, Collman RG, Bushman FD, Li H (2015) Power and sample-size estimation for microbiome studies using pairwise distances and PERMANOVA. Bioinformatics 31(15):2461–2468.  https://doi.org/10.1093/bioinformatics/btv183 CrossRefGoogle Scholar
  21. 21.
    Valdez R, Seidell JC, Ahn YI, Weiss KM (1993) A new index of abdominal adiposity as an indicator of risk for cardiovascular disease. A cross-population study. Int J Obes Relat Metab Disord 17:77–82Google Scholar
  22. 22.
    Kahn HS (2005) The lipid accumulation product performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison. BMC Cardiovasc Disord 5:26.  https://doi.org/10.1186/1471-2261-5-26 CrossRefGoogle Scholar
  23. 23.
    Shirai N, Suzuki H, Wada S (2005) Direct methylation from mouse plasma and from liver and brain homogenates. Anal Biochem 343:48–53.  https://doi.org/10.1016/j.ab.2005.04.037 CrossRefGoogle Scholar
  24. 24.
    Botelho PB, Guimarães JP, Mariano KR, Afonso MS, Koike MK, Lottenberg AMP, Castro IA et al (2015) Effect of echium oil combined with phytosterols on biomarkers of atherosclerosis in LDLr-knockout mice: Echium oil is a potential alternative to marine oils for use in functional foods. Eur J Lipid Sci Tech 117:1561–1568.  https://doi.org/10.1002/ejlt.201500004 CrossRefGoogle Scholar
  25. 25.
    Bilici M, Efe H, Arif Koroglu M, Avni Uydu H, Bekaroglu M, Deger O (2001) Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 64:43–51.  https://doi.org/10.1016/S0165-0327(00)00199-3 CrossRefGoogle Scholar
  26. 26.
    Mooi E, Sarstedt MA (2011) Concise guide to market research: the process, data, and methods using IBM SPSS statistics. Springer, BerlinCrossRefGoogle Scholar
  27. 27.
    Gomes AC, Hoffmann C, Mota JF (2018) The human gut microbiota: Metabolism and perspective in obesity. Gut Microbes.  https://doi.org/10.1080/19490976.2018.1465157 Google Scholar
  28. 28.
    Valdes AM, Walter J, Segal E, Spector TD et al (2018) Role of the gut microbiota in nutrition and health. BMJ 361:k2179.  https://doi.org/10.1136/bmj.k2179 CrossRefGoogle Scholar
  29. 29.
    Chen D, Yang Z, Chen X, Huang Y, Yin B, Guo F et al (2014) The effect of Lactobacillus rhamnosus hsryfm 1301 on the intestinal microbiota of a hyperlipidemic rat model. BMC Complement Altern Med 14(386):2014.  https://doi.org/10.1186/1472-6882-14-386 Google Scholar
  30. 30.
    Kumar PS, Griffen AL, Barton JA, Paster BJ, Moeschberger ML, Leys EJ (2003) New bacterial species associated with chronic periodontitis. J Dent Res 82:338–344.  https://doi.org/10.1177/154405910308200503 CrossRefGoogle Scholar
  31. 31.
    Bik EM, Long CD, Armitage GC, Loomer P, Emerson J, Mongodin EF et al (2010) Bacterial diversity in the oral cavity of 10 healthy individuals. ISME J 4:962–974.  https://doi.org/10.1038/ismej.2010.30 CrossRefGoogle Scholar
  32. 32.
    Zaura E, Keijser BJ, Huse SM (2009) Defining the healthy “core microbiome” of oral microbial communities. BMC Microbiol 9:259.  https://doi.org/10.1186/1471-2180-9-259 CrossRefGoogle Scholar
  33. 33.
    Kuehbacher T, Rehman A, Lepage P, Hellmig S, Fölsch UR, Schreiber S et al (2008) Intestinal TM7 bacterial phylogenies in active inflammatory bowel disease. J Med Microbiol 57:1569–1576.  https://doi.org/10.1099/jmm.0.47719-0 CrossRefGoogle Scholar
  34. 34.
    Elinav ET, Strowig AL, Kau J, Henao-Mejia J, Thais CA, Booth CJ et al (2011) NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745–757.  https://doi.org/10.1016/j.cell.2011.04.022 CrossRefGoogle Scholar
  35. 35.
    Guss AM, Roeselers G, Newton IL, Young CR, Klepac-Ceraj V, Lory S, Cavanaugh CM (2011) Phylogenetic and metabolic diversity of bacteria associated with cystic fibrosis. ISME J 5:20–29.  https://doi.org/10.1038/ismej.2010.88 CrossRefGoogle Scholar
  36. 36.
    Brinig MM, Lepp PW, Ouverney CC, Armitage GC, Relman DA (2003) Prevalence of bacteria of division TM7 in human subgingival plaque and their association with disease. Appl Environ Microbiol 69:1687–1694.  https://doi.org/10.1128/aem.69.3.1687-1694.2003 CrossRefGoogle Scholar
  37. 37.
    Flynn CR, Albaugh VL, Cai S, Cheung-Flynn J, Williams PE, Brucker RM et al (2015) Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun 6:7715.  https://doi.org/10.1038/ncomms8715 CrossRefGoogle Scholar
  38. 38.
    Casarin RC, Barbagallo A, Meulman T, Santos VR, Sallum EA, Nociti FH et al (2013) Subgingival biodiversity in subjects with uncontrolled type-2 diabetes and chronic periodontitis. J Periodontal Res 48:30–36.  https://doi.org/10.1111/j.1600-0765.2012.01498.x CrossRefGoogle Scholar
  39. 39.
    He M, Shi B (2017) Gut microbiota as a potential target of metabolic syndrome: the role of probiotics and prebiotics. Cell Biosci 7:54.  https://doi.org/10.1186/s13578-017-01831 CrossRefGoogle Scholar
  40. 40.
    Chávez-Carbajal A, Nirmalkar K, Pérez-Lizaur A, Hernández-Quiroz F, Ramírez-Del-Alto S, García-Mena J et al (2019) microbiota and predicted metabolic pathways in a sample of mexican women affected by obesity and obesity plus metabolic syndrome. Int J Mol Sci 20:2.  https://doi.org/10.3390/ijms20020438 CrossRefGoogle Scholar
  41. 41.
    Sotos M, Nadal I, Marti A, Martínez A, Martin-Matillas M, Campoy C et al (2008) Gut microbes and obesity in adolescents. Proc Nutr Soc 67:20.  https://doi.org/10.1017/S0029665108006290 CrossRefGoogle Scholar
  42. 42.
    Watanabe Y, Nagai F, Morotomi M (2012) Characterization of Phascolarctobacterium succinatutens sp. nov., an asaccharolytic, succinate-utilizing bacterium isolated from human feces. Appl Environ Microbiol 78:511–518.  https://doi.org/10.1128/AEM.06035-11 CrossRefGoogle Scholar
  43. 43.
    Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ et al (2006) Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 40:235–243CrossRefGoogle Scholar
  44. 44.
    Demigne C, Morand C, Levrat MA, Besson C, Moundras C, Rémésy C (1995) Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes. Br J Nutr 74:209–219CrossRefGoogle Scholar
  45. 45.
    Delzenne NM, Williams CM (2002) Prebiotics and lipid metabolism. Curr Opin Lipidol 13:61–67CrossRefGoogle Scholar
  46. 46.
    Chakraborti CK (2015) New-found link between microbiota and obesity. World J Gastrointest Pathophysiol 6:110–119.  https://doi.org/10.4291/wjgp.v6.i4.110 CrossRefGoogle Scholar
  47. 47.
    La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE (2010) Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 299:G440–G448.  https://doi.org/10.1152/ajpgi.00098.2010 CrossRefGoogle Scholar
  48. 48.
    Andoh A, Nishida A, Takahashi K, Inatomi O, Imaeda H, Bamba S et al (2016) Comparison of the gut microbial community between obese and lean peoples using 16S gene sequencing in a Japanese population. J Clin Biochem Nutr 59:65–70.  https://doi.org/10.3164/jcbn.15-152 CrossRefGoogle Scholar
  49. 49.
    Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM et al (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–298.  https://doi.org/10.1101/gr.126573.111 CrossRefGoogle Scholar
  50. 50.
    Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D et al (2012) Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491:254–258.  https://doi.org/10.1038/nature11465 CrossRefGoogle Scholar
  51. 51.
    Hu HJ, Park SG, Jang HB, Choi MK, Park KH, Kang JH et al (2015) Obesity alters the microbial community profile in korean adolescents. PLoS One 10:e0134333.  https://doi.org/10.1371/journal.pone.0134333 CrossRefGoogle Scholar
  52. 52.
    Flint HJ, Bayer EA, Rincon MT, Lamed R, White BA (2008) Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nature Rev Microbiol 6:121–131.  https://doi.org/10.1038/nrmicro1817 CrossRefGoogle Scholar
  53. 53.
    Bervoets L, Hoorenbeeck KV, Kortleven I, Lamed R, White BA et al (2013) Differences in gut microbiota composition between obese and lean children: a cross-sectional study. Pathogens 5:10.  https://doi.org/10.1186/1757-4749-5-10 Google Scholar
  54. 54.
    Durbán A, Abellán JJ, Latorre A, Moya A (2013) Effect of dietary carbohydrate restriction on an obesity-related Prevotella-dominated human fecal microbiota. Metagenomics 2:235722.  https://doi.org/10.4303/mg/235722 CrossRefGoogle Scholar
  55. 55.
    Damms-Machado A, Mitra S, Schollenberger AE, Kramer KM, Meile T, Königsrainer A et al (2015) Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int 2015:806248.  https://doi.org/10.1155/2015/806248 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Clinical and Sports Nutrition Research Laboratory (LABINCE), Faculty of NutritionFederal University of GoiasGoiâniaBrazil
  2. 2.Department of Food Sciences and Experimental Nutrition, School of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil

Personalised recommendations