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Effect of prebiotic fiber on physical function and gut microbiota in adults, mostly women, with knee osteoarthritis and obesity: a randomized controlled trial

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Abstract

Purpose

Obesity is a primary risk factor for knee osteoarthritis (OA). Prebiotics enhance beneficial gut microbes and can reduce body fat and inflammation. Our objective was to examine if a 6-month prebiotic intervention improved physical function in adults with knee osteoarthritis and obesity. We also measured knee pain, body composition, quality of life, gut microbiota, inflammatory markers, and serum metabolomics.

Methods

Adults (n = 54, mostly women) with co-morbid obesity (BMI > 30 kg/m2) and unilateral/bilateral knee OA were randomly assigned to prebiotic (oligofructose-enriched inulin; 16 g/day; n = 31) or isocaloric placebo (maltodextrin; n = 21) for 6 months. Performance based-tests, knee pain, quality of life, serum metabolomics and inflammatory markers, and fecal microbiota and short-chain fatty acids were assessed.

Results

Significant between group differences were detected for the change in timed-up-and-go test, 40 m fast paced walk test, and hand grip strength test from baseline that favored prebiotic over placebo. Prebiotic also reduced trunk fat mass (kg) at 6 months and trunk fat (%) at 3 months compared to placebo. There was a trend (p = 0.059) for reduced knee pain at 6 months with prebiotic versus placebo. In gut microbiota analysis, a total of 37 amplicon sequence variants differed between groups. Bifidobacterium abundance was positively correlated with distance walked in the 6-min walk test and hand grip strength. At 6 months, there was a significant separation of serum metabolites between groups with upregulation of phenylalanine and tyrosine metabolism with prebiotic.

Conclusion

Prebiotics may hold promise for conservative management of knee osteoarthritis in adults with obesity and larger trials are warranted.

Clinical Trial Registration

Clinicaltrials.gov/study/NCT04172688.

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Data availability

The data and materials of the current study is available from the corresponding author upon reasonable request.

References

  1. Georgiev T, Angelov A (2019) Modifiable risk factors in knee osteoarthritis: treatment implications. Rheumatol Int 39:1145–1157. https://doi.org/10.1007/s00296-019-04290-z

    Article  PubMed  Google Scholar 

  2. Cleveland RJ, Nelson AE, Callahan L (2019) Knee and hip osteoarthritis as predictors of premature death: a review of the evidence. Clin Exp Rheumatol 37(Suppl 1):24–30

    PubMed  PubMed Central  Google Scholar 

  3. Liu M, Jin F, Xiacong Y, Zhongxin Z (2022) Disease burden of osteoarthritis of the knee and hip due to a high body mass index in China and the USA: 1990–2019 findings from the global burden of disease study 2019. BMC Musculoskelet Disord 23:63. https://doi.org/10.1186/s12891-022-05027-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yedlin E, Cisternas M (2018) United States bone and joint initiative: the burden of musculoskeletal diseases in the United States (BMUS), Fourth edition, Forthcoming Rosemont, IL

  5. Batushansky A, Zhu S, Komaravolu RK, South S, Mehta-D’Souza P, Griffin T (2022) Fundamentals of OA. an initiative of osteoarthritis and cartilage. obesity and metabolic factors in OA. Osteoarthr Cartil 30:501–515. https://doi.org/10.1016/j.joca.2021.06.013

    Article  CAS  Google Scholar 

  6. Hart D (2022) Osteoarthritis as an umbrella term for different subsets of humans undergoing joint degeneration: the need to address the differences to develop effective conservative treatments and prevention strategies. Int J Mol Sci 23(23):153. https://doi.org/10.3390/ijms232315365

    Article  Google Scholar 

  7. Collins KH, Hart DA, MacDonald GZ, Reimer RA, Herzog W (2018) Obesity, metabolic syndrome, and musculoskeletal disease: common inflammatory pathways suggest a central role for loss of muscle integrity. Front Physiol 9:112. https://doi.org/10.3389/fphys.2018.00112

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gibson GR, Hutkins R, Sanders ME et al (2017) Expert consensus document: The international scientific association for probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol 14:491–502. https://doi.org/10.1038/nrgastro.2017.75

    Article  PubMed  Google Scholar 

  9. Gill PA, van Zelm MC, Muir JG, Gibson P (2018) Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther 48:15–34. https://doi.org/10.1111/apt.14689

    Article  CAS  PubMed  Google Scholar 

  10. Zheng L, Kelly CJ, Battista KD et al (2017) Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor-dependent repression of claudin-2. J Immunol 199:2976–2984. https://doi.org/10.4049/jimmunol.1700105

    Article  CAS  PubMed  Google Scholar 

  11. McLoughlin RF, Berthon BS, Jensen ME, Baines KJ, Wood L (2017) Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr 106:930–945. https://doi.org/10.3945/ajcn.117.156265

    Article  CAS  PubMed  Google Scholar 

  12. Kellow NJ, Coughlan MT, Reid C (2014) Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. Br J Nutr 111:1147–1161. https://doi.org/10.1017/S0007114513003607

    Article  CAS  PubMed  Google Scholar 

  13. Parnell JA, Reimer RA (2009) Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr 89:1751–1759. https://doi.org/10.3945/ajcn.2009.27465

    Article  CAS  PubMed  Google Scholar 

  14. Nicolucci AC, Hume MP, Martinez I, Mayengbam S, Walter J, Reimer RA (2017) Prebiotics reduce body fat and alter intestinal microbiota in children who are overweight or with obesity. Gastroenterology 153:711–722. https://doi.org/10.1053/j.gastro.2017.05.055

    Article  PubMed  Google Scholar 

  15. Rios JL, Bomhof MR, Reimer RA, Hart DA, Herzog W (2019) Protective effect of prebiotic and exercise intervention on knee health in a rat model of diet-induced obesity. Sci Rep 9:3893. https://doi.org/10.1038/s41598-019-40601-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Schott EM, Farnsworth CW, Grier A et al (2018) Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight. https://doi.org/10.1172/jci.insight.95997

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kellgren JH, Lawrence J (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502. https://doi.org/10.1136/ard.16.4.494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fortuna R, Hart DA, Sharkey KA, Schachar RA, Johnston K, Reimer R (2021) Effect of a prebiotic supplement on knee joint function gut microbiota and inflammation in adults with co-morbid obesity and knee osteoarthritis: study protocol for a randomized controlled trial. Trials 22:255. https://doi.org/10.1186/s13063-021-05212-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dobson F, Hinman RS, Roos EM et al (2013) OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthr Cartil 21:1042–1052. https://doi.org/10.1016/j.joca.2013.05.002

    Article  CAS  Google Scholar 

  20. Melamud E, Vastag L, Rabinowitz J (2010) Metabolomic analysis and visualization engine for LC-MS data. Anal Chem 82:9818–9826. https://doi.org/10.1021/ac1021166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Clasquin MF, Melamud E, Rabinowitz J (2012) LC-MS data processing with MAVEN: a metabolomic analysis and visualization engine. Curr Protoc Unit 14:11. https://doi.org/10.1002/0471250953.bi1411s37

    Article  Google Scholar 

  22. Bolyen E, Rideout JR, Dillon MR et al (2019) Reproducible interactive scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 37:852–857. https://doi.org/10.1038/s41587-019-0209-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mayengbam S, Lambert JE, Parnell JA et al (2019) Impact of dietary fiber supplementation on modulating microbiota-host-metabolic axes in obesity. J Nutr Biochem 64:228–236. https://doi.org/10.1016/j.jnutbio.2018.11.003

    Article  CAS  PubMed  Google Scholar 

  24. Weiss S, Zu ZZ, Peddada S et al (2017) Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome 5:27. https://doi.org/10.1186/s40168-017-0237-y

    Article  PubMed  PubMed Central  Google Scholar 

  25. McAlindon TE, Bannuru RR, Sullivan MC et al (2014) OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil 22:363–388. https://doi.org/10.1016/j.joca.2014.01.003

    Article  CAS  Google Scholar 

  26. Yu XH, Yang YQ, Cao RR, Lei S (2021) The causal role of gut microbiota in development of osteoarthritis. Osteoarthr Cartil 29:1741–1750. https://doi.org/10.1016/j.joca.2021.08.003

    Article  Google Scholar 

  27. He Y, Wu W, Wu S et al (2018) Linking gut microbiota metabolic syndrome and economic status based on a population-level analysis. Microbiome 6:172. https://doi.org/10.1186/s40168-018-0557-6

    Article  PubMed  PubMed Central  Google Scholar 

  28. Huang ZY, Chen J, Li BL et al (2020) Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice. Osteoarthritis 79:646–656. https://doi.org/10.1136/annrheumdis-2019-216471

    Article  CAS  Google Scholar 

  29. Guo S, Guo Y, Ergun A, Lu L, Walker WA, Gangulit K (2015) Secreted metabolites of Bifidobacterium infantis and Lactobacillus acidophilus protect immature human enterocytes from IL-1β-induced inflammation: a transcription profiling analysis. PLoS ONE. https://doi.org/10.1371/journal.pone.0124549

    Article  PubMed  PubMed Central  Google Scholar 

  30. Li B, Ding M, Liu X et al (2022) Bifidobacterium breve CCFM1078 alleviates collagen-induced arthritis in rats via modulating the gut microbiota and repairing the intestinal barrier damage. J Agric Food Chem 70:14665–14678. https://doi.org/10.1021/acs.jafc.2c04602

    Article  CAS  PubMed  Google Scholar 

  31. Cani PD, Amar J, Igliesias MA et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772. https://doi.org/10.2337/db06-1491

    Article  CAS  PubMed  Google Scholar 

  32. Loeser R, Arbeeva L, Kelley K et al (2022) Association of increased serum lipopolysaccharide but not microbial dysbiosis with obesity-related osteoarthritis. Arthritis Rheumatol 74:227–236. https://doi.org/10.1002/art.41955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Parnell JA, Klancic T, Reimer R (2017) Oligofructose decreases serum lipopolysaccharide and plasminogen activator inhibitor-1 in adults with overweight/obesity. Obes (Silver Spring) 25(3):510–513. https://doi.org/10.1002/oby.21763

    Article  CAS  Google Scholar 

  34. Chang PV, Hao L, Offermanns S, Medzhitov R (2014) The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci 111:2247–2252. https://doi.org/10.1073/pnas.1322269111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Towle CA, Hung HH, Bonassar LJ, Treadwell BV, Mangham D (1997) Detection of interleukin-1 in the cartilage of patients with osteoarthritis: a possible autocrine/paracrine role in pathogenesis. Osteoarthr Cartil 5:293–300. https://doi.org/10.1016/s1063-4584(97)80008-8

    Article  CAS  Google Scholar 

  36. Joosten LAB, Smeets RL, Koenders MI et al (2004) Interleukin-18 promotes joint inflammation and induces interleukin-1-driven cartilage destruction. Am J Pathol 165:959–967. https://doi.org/10.1016/S0002-9440(10)63357-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mailhot B, Christin M, Tessandier N et al (2020) Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases. J Exp Med. https://doi.org/10.1084/jem.20191430

    Article  PubMed  PubMed Central  Google Scholar 

  38. Milani C, Duranti S, Bottacini F et al (2017) The first microbial colonizers of the human gut: composition activities and health implications of the infant gut microbiota. Microbiol Mol Biol Rev 81:e00036-e117. https://doi.org/10.1128/MMBR.00036-17

    Article  PubMed  PubMed Central  Google Scholar 

  39. Dai Z, Niu J, Zhang Y, Jacques P, Felson D (2017) Dietary intake of fibre and risk of knee osteoarthritis in two US prospective cohorts. Ann Rheum Dis 76:1411–1419. https://doi.org/10.1136/annrheumdis-2016-210810

    Article  CAS  PubMed  Google Scholar 

  40. Dai Z, Jafarzadeh SR, Niu J, Felson DT, Jacques PF, Li S, Zhang Y (2018) Body mass index mediates the association between dietary fiber and symptomatic knee osteoarthritis in the osteoarthritis initiative and the framingham osteoarthritis study. J Nutr 148:1961–1967. https://doi.org/10.1093/jn/nxy231

    Article  PubMed  PubMed Central  Google Scholar 

  41. Liu T, Xu C, Driban JB et al (2023) Whole grain consumption and risk of radiographic knee osteoarthritis: a prospective study from the osteoarthritis initiative. Rheumatology 62:1834–1840. https://doi.org/10.1093/rheumatology/keac517

    Article  PubMed  Google Scholar 

  42. Pallister T, Jackson MA, Martin TC et al (2017) Hippurate as a metabolomic marker of gut microbiome diversity: modulation by diet and relationship to metabolic syndrome. Sci Rep 7:13670. https://doi.org/10.1038/s41598-017-13722-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Arias-Barrau E, Olivera ER, Luengo JM et al (2004) The homogentisate pathway: a central catabolic pathway involved in the degradation of l-phenylalanine l-tyrosine and 3-hydroxyphenylacetate in Pseudomonas putida. J Bacteriol 186:5062–5077. https://doi.org/10.1128/JB.186.15.5062-5077.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Alkhaldy A, Edwards CA, Combet E (2019) The urinary phenolic acid profile varies between younger and older adults after a polyphenol-rich meal despite limited differences in in vitro colonic catabolism. Eur J Nutr 58:1095–1111. https://doi.org/10.1007/s00394-018-1625-1

    Article  CAS  PubMed  Google Scholar 

  45. Williams HRT, Cox IJ, Walker DG et al (2010) Differences in gut microbial metabolism are responsible for reduced hippurate synthesis in Crohn’s disease. BMC Gastroenterol 10:108. https://doi.org/10.1186/1471-230X-10-108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Raffner AR, Wearsh BA, Cominelli P, F, Rodriguez-Palacios A, (2022) Validity of food additive maltodextrin as placebo and effects on human gut physiology: systematic review of placebo-controlled clinical trials. Eur J Nutr 61:2853–2871. https://doi.org/10.1007/s00394-022-02802-5

    Article  CAS  Google Scholar 

  47. Skou ST, Roos E (2017) Good life with osteoarthritis in Denmark (GLA:D): evidence-based education and supervised neuromuscular exercise delivered by certified physiotherapists nationwide. BMC Musculoskelet Disord 18:72. https://doi.org/10.1186/s12891-017-1439-y

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors acknowledge Dr. Rachel Schachar and Dr. Kelly Johnston for assistance with recruitment. We thank Beneo GmbH, Mannheim, Germany for providing the prebiotic and placebo product. Metabolomics data were acquired by Marija Drikic at the Calgary Metabolomics Research Facility, which is supported by the International Microbiome Centre and the Canada Foundation for Innovation.

Funding

This work was supported by a Weston Foundation Microbiome Initiative Grant and a McCaig Encore Catalyst Grant. RF was supported by an Alberta Innovates Postdoctoral Fellowship and a Dr. Cy Frank Trainee Award in Nutrition, Bone and Joint Health. WW was supported by an Eyes High Postdoctoral Fellowship.

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Authors and Affiliations

Authors

Contributions

RF, RAR, DAH, and KAS conceived the study; RF conducted the trial; WW conducted the gut microbiota analysis; SM conducted the metabolomics analysis; EWNT conducted the SCFA analysis; KS conducted the diet analysis; RF and RAR drafted the manuscript; all authors reviewed and approved the final submitted manuscript.

Corresponding author

Correspondence to Raylene A. Reimer.

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Conflict of interest

RF, WW, SM, EWNT, KS, KAS, DAH declare no conflict of interest. RAR has received honoraria from Beneo for presentations distinct from this work.

Ethical approval and consent to participate

The study protocol was approved by the Conjoint Health Research Ethics Board of the University of Calgary (REB17-2363). This study was registered at www.clinicaltrial.gov NCT04172688. Informed consent was obtained from all participants.

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Fortuna, R., Wang, W., Mayengbam, S. et al. Effect of prebiotic fiber on physical function and gut microbiota in adults, mostly women, with knee osteoarthritis and obesity: a randomized controlled trial. Eur J Nutr (2024). https://doi.org/10.1007/s00394-024-03415-w

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