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Association of Fructo-oligosaccharides and Arginine Improves Severity of Mucositis and Modulate the Intestinal Microbiota

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Abstract

Mucositis is defined as inflammatory and ulcerative lesions along of the gastrointestinal tract that leads to the imbalance of the intestinal microbiota. The use of compounds with action on the integrity of the intestinal epithelium and their microbiota may be a beneficial alternative for the prevention and/or treatment of mucositis. So, the aim of this study was to evaluate the effectiveness of the association of fructo-oligosaccharides (FOS) and arginine on intestinal damage in experimental mucositis. BALB/c mice were randomized into five groups: CTL (without mucositis + saline), MUC (mucositis + saline), MUC + FOS (mucositis + supplementation with FOS—1st until 10th day), MUC + ARG (mucositis + supplementation with arginine—1st until 10th day), and MUC + FOS + ARG (mucositis + supplementation with FOS and arginine—1st until 10th day). On the 7th day, mucositis was induced with an intraperitoneal injection of 300 mg/kg 5-fluorouracil (5-FU), and after 72 h, the animals were euthanized. The results showed that association of FOS and arginine reduced weight loss and oxidative stress (P < 0.05) and maintained intestinal permeability and histological score at physiological levels. The supplementation with FOS and arginine also increased the number of goblet cells, collagen area, and GPR41 and GPR43 gene expression (P < 0.05). Besides these, the association of FOS and arginine modulated intestinal microbiota, leading to an increase in the abundance of the genera Bacteroides, Anaerostipes, and Lactobacillus (P < 0.05) in relation to increased concentration of propionate and acetate. In conclusion, the present results show that the association of FOS and arginine could be important adjuvants in the prevention of intestinal mucositis probably due to modulated intestinal microbiota.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank the Pro Reitoria de Pesquisa da UFMG (PRPQ).

Funding

This study received grants from Conselho Nacional de Desenvolvimento Científico e Tecnoógico (CNPq) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG). Simone Odília Antunes Fernandes and Valbert Nascimento Cardoso are supported by a grant from the FAPEMIG (Rede Mineira de Pesquisa Translacional em Imunobiológicos e Biofármacos no Câncer [REMITRIBIC, RED-00031–21]) and CNPq (303506/2019-9). Simone Vasconcelos Generoso is supported by a grant from the CNPq (308226/2019–4).

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MERA designed the study, conducted all experiments, and wrote the main text of the manuscript; LMT wrote the main text of the manuscript; SVG wrote the main text of the manuscript and analyzed the microbiota results; PCLL and JIAL performed the analysis of oxidative stress and receptors; DCR and GDC analyzed histopathology and immunohistochemistry; TFS, RDOC, and VACA performed the analysis of the intestinal microbiota; GGC and JSO analyzed the production of short-chain fatty acids; VNC guided the work and wrote the main text of the manuscript; SOA collaborated in the analysis of intestinal permeability. All authors reviewed and approved the manuscript.

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Correspondence to Valbert Nascimento Cardoso.

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Andrade, M.E.R., Trindade, L.M., Leocádio, P.C.L. et al. Association of Fructo-oligosaccharides and Arginine Improves Severity of Mucositis and Modulate the Intestinal Microbiota. Probiotics & Antimicro. Prot. 15, 424–440 (2023). https://doi.org/10.1007/s12602-022-10032-8

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