Modulation of gut microbiota through nutritional interventions in Behçet's syndrome patients (the MAMBA study): study protocol for a randomized controlled trial

Giuditta Pagliai, Monica Dinu, Claudia Fiorillo, Matteo Becatti, Silvia Turroni, Giacomo Emmi, Francesco Sofi, Giuditta Pagliai, Monica Dinu, Claudia Fiorillo, Matteo Becatti, Silvia Turroni, Giacomo Emmi, Francesco Sofi

Abstract

Background: Behçet's syndrome (BS) is a systemic inflammatory disorder of unknown etiology, and it is characterized by a wide range of potential clinical manifestations. Recent evidence suggests that the gut microbiota (GM) in BS has low biodiversity with a significant depletion in butyrate producers. The aim of the present project is to investigate whether a dietary intervention could ameliorate the clinical manifestations and modulate the GM of individuals with BS.

Methods: This is a randomized, open, cross-over study that involves 90 individuals with BS, who will be randomly assigned to one of three different diets for 3 months: a lacto-ovo-vegetarian diet (VD), a Mediterranean diet (MD), or a Mediterranean diet supplemented with butyrate (MD-Bt). The VD will contain inulin-resistant and resistant-starch-rich foods, eggs, and dairy in addition to plant-based food, but it will not contain meat, poultry, or fish. The MD will contain all food categories and will provide two portions per week of fish and three portions per week of fresh and processed meat. The MD-Bt will be similar to the MD but supplemented with 1.8 g/day of oral butyrate. The three different diets will be isocaloric and related to the participants' nutritional requirements. Anthropometric measurements, body composition, blood, and fecal samples will be obtained from each participant at the beginning and the end of each intervention phase. The primary outcomes will be represented by the change from baseline of the BS gastrointestinal and systemic symptoms. Changes from baseline in GM composition, short-chain fatty acid (SCFA) production, and the inflammatory and antioxidant profile will be considered as secondary outcomes.

Discussion: BS is a rare disease, and, actually, not all the available treatments are target therapies. A supportive treatment based on dietary and lifestyle issues, able to restore immune system homeostasis, could have a high impact on cost sustainability for the treatment of such a chronic and disabling inflammatory condition.

Trial registration: clinicaltrials.gov: NCT03962335. Registered on 21 May 2019.

Keywords: Gut microbiota; Mediterranean diet; Short-chain fatty acids; Vegetarian diet.

Conflict of interest statement

The Authors declare that they have no competing interests and the research is not being supported by any commercial organization.

Figures

Fig. 1
Fig. 1
Schedule of enrollment, interventions, and assessments for participants. SSS, Symptom Severity Scale; GAI, Global Assessment of Improvement Scale; BDCA, Behçet Disease Current Activity Form; mo, month
Fig. 2
Fig. 2
Study design. VD, vegetarian diet; MD, Mediterranean diet; MD-Bt, Mediterranean diet supplemented with butyrate

References

    1. Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behçet’s disease: a review. World J Gastroenterol. 2015;21:3801–3812. doi: 10.3748/wjg.v21.i13.3801.
    1. Emmi G, Bettiol A, Silvestri E, Di Scala G, Becatti M, Fiorillo C, Prisco D. Vascular Behçet’s syndrome: an update. Intern Emerg Med. 2019;14(5):645–652. doi: 10.1007/s11739-018-1991-y.
    1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11. doi: 10.1002/art.37715.
    1. Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, et al. Behçet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015;14:269–276. doi: 10.1016/j.autrev.2014.11.009.
    1. Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136:65–80. doi: 10.1053/j.gastro.2008.10.080.
    1. Candela M, Biagi E, Turroni S, Maccaferri S, Figini P, Brigidi P. Dynamic efficiency of the human intestinal microbiota. Crit Rev Microbiol. 2015;41(2):165-71.
    1. Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375(24):2369–2379. doi: 10.1056/NEJMra1600266.
    1. Kosiewicz M, Dryden GW, Chhabra A, Alard P. Relationship between gut microbiota and development of T cell associated disease. FEBS Lett. 2014;5793:224–225.
    1. Emmi G, Silvestri E, Della Bella C, Grassi A, Benagiano M, Cianchi F, et al. Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease. Medicine (Baltimore) 2016;95(49):e5516. doi: 10.1097/MD.0000000000005516.
    1. Zmora N, Suez J, Elinav E. You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol. 2019;16(1):35–56. doi: 10.1038/s41575-018-0061-2.
    1. Kolodziejczyk AA, Zheng D, Elinav E. Diet-microbiota interactions and personalized nutrition. Nat Rev Microbiol. 2019;17(12):742–753. doi: 10.1038/s41579-019-0256-8.
    1. Dinu M, Abbate R, Gensini GF, Casini A, Sofi F. Vegetarian, vegan diets and multiple health outcomes: a systematic review with meta-analysis of observational studies. Crit Rev Food Sci Nutr. 2017;57:3640–3649. doi: 10.1080/10408398.2016.1138447.
    1. Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017;8(2):172–184. doi: 10.1080/19490976.2017.1290756.
    1. Kabeerdoss J, Devi RS, Mary RR, Ramakrishna BS. Faecal microbiota composition in vegetarians: comparison with omnivores in a cohort of young women in southern India. Br J Nutr. 2012;108:953,957. doi: 10.1017/S0007114511006362.
    1. Haro C, Montes-Borrego M, Rangel-Zúñiga OA, Alcalá-Díaz JF, Gómez-Delgado F, Pérez-Martínez P, et al. Two healthy diets modulate gut microbial community improving insulin sensitivity in a human obese population. J Clin Endocrinol Metab. 2016;101:233–242. doi: 10.1210/jc.2015-3351.
    1. De Filippis F, Pellegrini N, Vannini L, Jeffrey IB, La Storia A, Laghi L, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016;65(11):1812–1821. doi: 10.1136/gutjnl-2015-309957.
    1. Candela M, Maccaferri S, Turroni S, Carnevali P, Brigidi P. Functional intestinal microbiome, new frontiers in prebiotic design. Int J Food Microbiol. 2010;140:93–101. doi: 10.1016/j.ijfoodmicro.2010.04.017.
    1. Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S, et al. Gut microbiota and extreme longevity. Curr Biol. 2016;26(11):1480–1485. doi: 10.1016/j.cub.2016.04.016.
    1. Munoz-Gonzalez I, Jiménez-Girón A, Martín-Álvarez PJ, Bartolomé B, Moreno-Arribas MV. Profiling of microbial-derived phenolic metabolites in human faces after moderate red wine intake. J Agr Food Chem. 2013;61:9470–9479. doi: 10.1021/jf4025135.
    1. Whittaker A, Sofi F, Luisi ML, Rafanelli E, Fiorillo C, Becatti M, et al. An organic khorasan wheat-based replacement diet improves risk profile of patients with acute coronary syndrome: a randomized crossover trial. Nutrients. 2015;7(5):3401–3415. doi: 10.3390/nu7053401.
    1. Whittaker A, Dinu M, Cesari F, Gori AM, Fiorillo C, Becatti M, et al. A khorasan wheat-based replacement diet improves risk profile of patients with type 2 diabetes mellitus (T2DM): a randomized crossover trial. Eur J Nutr. 2017;56(3):1191–1200. doi: 10.1007/s00394-016-1168-2.
    1. Sofi F, Dinu M, Pagliai G, Cesari F, Gori AM, Sereni A, et al. Low-calorie vegetarian versus Mediterranean diets for reducing body weight and improving cardiovascular risk profile: CARDIVEG study (Cardiovascular prevention with vegetarian diet) Circulation. 2018;137(11):1103–1113. doi: 10.1161/CIRCULATIONAHA.117.030088.
    1. Gueraud F, Peiro G, Bernard H, Alary J, Creminon C, Debrauwer L, et al. Enzyme immunoassay for a urinary metabolite of 4-hydroxynonenal as a marker of lipid peroxidation. Free Radic Biol Med. 2006;40(1):54–62. doi: 10.1016/j.freeradbiomed.2005.08.011.
    1. Pedersen N, Ankersen DV, Felding M, Wachmann H, Végh Z, Molzen L, et al. Low-FODMAP diet reduces irritable bowel symptoms in patients with inflammatory bowel disease. World J Gastroenterol. 2017;23(18):3356–3366. doi: 10.3748/wjg.v23.i18.3356.
    1. Masella AP, Bartram AK, Truszkowski JM, Brown DG, Neufeld JD. PANDAseq: paired-end assembler for illumina sequences. BMC Bioinformatics. 2012;13:31. doi: 10.1186/1471-2105-13-31.
    1. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335–336. doi: 10.1038/nmeth.f.303.
    1. Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010;26(19):2460–2461. doi: 10.1093/bioinformatics/btq461.
    1. Mumcu G, Direskeneli H. Triggering agents and microbiome as environmental factors on Behçet's syndrome. Intern Emerg Med. 2019;14(5):653–660. doi: 10.1007/s11739-018-2000-1.
    1. Ye Z, Zhang N, Wu C, Zhang X, Wang Q, Huang X, et al. A metagenomic study of the gut microbiome in Behcet’s disease. Microbiome. 2018;6:135. doi: 10.1186/s40168-018-0520-6.
    1. Pagliai G, Russo E, Niccolai E, Dinu M, Di Pilato V, Magrini A, et al. Influence of a 3-month low calorie Mediterranean diet compared to the vegetarian diet on human gut microbiota and SCFA: the CARDIVEG study. Eur J Nutr. 2019. 10.1007/s00394-019-02050-0.

Source: PubMed

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