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

Andrade, Meire Cristina Nogueira de; Trindade, Luísa Martins; Leocádio, Paola Caroline Lacerda; Leite, Jacqueline Isaura Alvarez; Reis, Diego Carlos dos; Cassali, Geovanni Dantas; Silva, Tales Fernando da; Carvalho, Rodrigo Dias de Oliveira; Azevedo, Vasco; Cavalcante, Gregório Grama; Oliveira, Jamil S.; Fernandes, Simone Odília Antunes; Generoso, S.V.; Cardoso, Valbert Nascimento

doi:10.1007/s12602-022-10032-8

Cited by 11 publications

(6 citation statements)

References 69 publications

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“…Likewise, no signi cant variation in microbiota composition, richness and diversity was observed following probiotic administration, even though the microbiota of CEC15-treated mice seemed closer to that of control mice than those treated with strain EcN. As expected, 5-FU administration led to a consistent in ammatory process in the ileum which was characterized by excessive weight loss, increase in intestinal permeability, neutrophils in ltration, and an accentuated destruction of ileal epithelial structure, as it has been reported by many studies before [106, 107,110]. No strain was able to prevent weight loss, a result that is not surprising given the aggressive nature of the 5-FU therapy.…”

Section: Discussionsupporting

confidence: 76%

“…To assess and compare their health effects, CEC15 and EcN strains were also tested in a mice 5-FU mucositis model. The reason for selecting this model is its high severity, which would enable the observation of notable protective effects promoted by any potential probiotic strains [4,104,105] and the fact that it is a well-established model [106][107][108][109][110]. Furthermore, it is crucial to emphasize the absence of studies assessing the impact of both EcN and CEC15 on the 5-FU-induced intestinal mucositis model, with the exception of two studies evaluating the effects of EcN supernatant [111,112].…”

Section: Discussionmentioning

confidence: 99%

“…An average of 50 mg of feces was used and the DNA extraction was performed with the QIAamp DNA stool Mini kit (QIAGEN) following the manufacture's instruction. Library preparation and sequencing were performed as described before [107]. Bioinformatic analysis were performed using the EasyAmplicon script [155] where the reads were merged, had the primers removed, were dereplicated, and the chimeras removed with VSEARCH [156], the processed reads were clustered in operational taxonomic units (OTUs) and analyzed by alpha and beta diversity with USEARCH [157].…”

Section: S Rrna Amplicon Metagenome Analysismentioning

confidence: 99%

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Comprehensive Probiogenomics Analysis of the Commensal Escherichia Coli CEC15 as a Potential Probiotic Strain

Silva

Glória

Sousa

et al. 2023

Preprint

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Background: Probiotics have gained attention for their potential maintaining gut and immune homeostasis. They have been found to confer protection against pathogen colonization, possess immunomodulatory effects, enhance gut barrier functionality, and mitigate inflammation. However, a thorough understanding of the unique mechanisms of effects triggered by individual strains is necessary to optimize their therapeutic efficacy. Probiogenomics, involving high-throughput techniques, can help identify uncharacterized strains and aid in the rational selection of new probiotics. This study evaluates the potential of the Escherichia coli CEC15 strain as a probiotic through in silico, in vitro, and in vivo analyses, comparing it to the reference E. coli Nissle 1917. Genomic analysis was conducted to identify traits with potential beneficial activity and to assess the safety of each strain (genomic islands, bacteriocin production, antibiotic resistance, production of proteins involved in host homeostasis, and proteins with adhesive properties). In vitro studies assessed survival in gastrointestinal simulated conditions and adhesion to cultured human intestinal cells. Safety was evaluated in BALB/c mice, monitoring the impact of E. coliconsumption on clinical signs, intestinal architecture, intestinal permeability, and fecal microbiota. Additionally, the protective effects of both strains were assessed in a murine model of 5-FU-induced mucositis. Results:CEC15 mitigates inflammation, reinforces intestinal barrier and modulates intestinal microbiota. In silico analysis revealed fewer pathogenicity-related traits in CEC15, when compared to Nissle 1917, with fewer toxin-associated genes and no gene suggesting the production of colibactin (a genotoxic agent). The majority of predicted antibiotic-resistance genes were neither associated with actual resistance, nor with transposable elements. The genome of CEC15 strain encodes proteins related to stress tolerance and to adhesion, in line with its better survival during digestion and higher adhesion to intestinal cells, when compared to Nissle 1917. Moreover, CEC15 exhibited beneficial effects on mice and its intestinal microbiota, both in healthy animals and against 5FU-induced intestinal mucositis. Conclusions: These findings suggest that the CEC15 strain holds promise as a probiotic, capable of modulating the intestinal microbiota, providing immunomodulatory and anti-inflammatory effects, and reinforcing the intestinal barrier. These findings may have implications for the treatment of gastrointestinal disorders, particularly inflammatory bowel disease.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: S Rrna Amplicon Metagenome Analysismentioning

confidence: 99%

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Comprehensive Probiogenomics Analysis of the Commensal Escherichia Coli CEC15 as a Potential Probiotic Strain

Silva

Glória

Sousa

et al. 2023

Preprint

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“…This is because the lower part of the small intestine is more susceptible to the effects of intestinal bacteria that are abundant in the cecum and large intestine. Anticancer treatment with 5-fluorouracil shows that enteritis mainly occurs in the ileum, which contains more intestinal bacteria (Andrade et al 2023;Jonan et al 2022). In this study, the damage was more pronounced in the ileal region because of the same effect of the intestinal bacteria.…”

Section: Discussionsupporting

confidence: 45%

Effect of echinacoside as a palliative for irinotecan-induced intestinal mucositis

Otsuki,

Jonan,

Tsujii

et al. 2023

IPh

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Irinotecan, an anticancer drug, causes severe delayed diarrhea due to its active metabolite, SN-38, which damages the intestinal mucosa. This diarrhea may lead to the discontinuation of anticancer therapy in clinical practice. Therefore, in this study, we aimed to elucidate the pathogenesis of irinotecan-induced intestinal inflammation. We examined the effects of echinacoside, which has been reported to reduce LPS (lipopolysaccharide)-induced apoptosis and inflammation. We administered irinotecan (75 mg/kg) to sevenweek-old male BALB/c mice intraperitoneally once daily for 4 d; a daily decrease in body weight, and no diarrhea was observed. Necropsies were performed 24 and 72 h after the last dose. Irinotecan caused cellular damage in the small intestine, particularly the ileum. After 72 h, a significant increase in myeloperoxidase activity was observed in the ileum. Concomitant oral administration of echinacoside (500 and 1000 mg/kg) with irinotecan significantly prevented weight loss and cellular damage in the ileal region. These results suggested the role of intestinal bacteria as previously reported with 5-FU-induced enteritis. The increased rate of deconjugation by β-glucuronidase may have increased the direct damage caused by SN-38. Additionally, irinotecan caused less histological damage to the large intestine than to the small intestine, possibly explaining the clinical absence of diarrhea. In conclusion, concomitant administration of echinacoside significantly inhibited the severity of irinotecan-induced intestinal inflammation, indicating their usefulness against irinotecan-induced enteritis.

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“…Studies have shown decreased crucial TJ proteins, such as ZO-1, in mucositis (54,55). Additionally, its depletion corresponds to an increase in intestinal permeability and a decrease in transepithelial resistance.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin improves intestinal mucositis induced by 5-fluorouracil in mice by modulating the and epithelial barrier and inflammatory signaling pathways

Vital

Pires

Gallotti

et al. 2023

Preprint

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Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1β, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3 signaling pathways.

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

Cited by 11 publications

References 69 publications

Comprehensive Probiogenomics Analysis of the Commensal Escherichia Coli CEC15 as a Potential Probiotic Strain

Comprehensive Probiogenomics Analysis of the Commensal Escherichia Coli CEC15 as a Potential Probiotic Strain

Effect of echinacoside as a palliative for irinotecan-induced intestinal mucositis

Atorvastatin improves intestinal mucositis induced by 5-fluorouracil in mice by modulating the and epithelial barrier and inflammatory signaling pathways

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