Paraprobiotic Lacticaseibacillus rhamnosus Protects Intestinal Damage in an Experimental Murine Model of Mucositis.

Intestinal mucositis (IM) is a common side effect resulting from cancer treatment. However, the management so far has not been very effective. In the last years, the role of the gut microbiota in the development and severity of mucositis has been studied. Therefore, the use of probiotics and paraprobiotics could have a potential therapeutic effect on IM. The aim of our study was to investigate the impact of the administration of Lacticaseibacillus rhamnosus (L. rhamnosus) CGMCC1.3724 and the paraprobiotic on IM in mice. For 13 days, male Balb/c mice were divided into six groups: control (CTL) and mucositis (MUC)/0.1 mL of saline; CTL LrV and MUC LrV/0.1 mL of 108 CFU of viable Lr; CTL LrI and MUC LrI/0.1 mL of 108 CFU of inactivated Lr. On the 10th day, mice from the MUC, MUC LrV, and MUC LrI groups received an intraperitoneal injection (300 mg/kg) of 5-fluorouracil to induce mucositis. The results showed that the administration of the chemotherapeutic agent increased the weight loss and intestinal permeability of the animals in the MUC and MUC LrV groups. However, administration of paraprobiotic reduced weight loss and maintained PI at physiological levels. The paraprobiotic also preserved the villi and intestinal crypts, reduced the inflammatory infiltrate, and increased the mucus secretion, Muc2 gene expression, and Treg cells frequency.

Relationship between Sarcopenia and mTOR Pathway in Patients with Colorectal Cancer: Preliminary Report.

Sarcopenia is a syndrome characterized by loss of muscle mass and strength that impacts clinical outcomes and mortality in cancer patients. Although the molecular pathways involved in sarcopenia are not fully elucidated, the decrease in protein synthesis rate appears to be one of the most important events. The objective of this study was to investigate the relationship between sarcopenia and mTOR signaling pathway in patients undergoing colorectal resection surgery. Three groups of patients were assessed: 1) the control group (no cancer, no sarcopenia), 2) the cancer non-sarcopenic group and 3) the cancer sarcopenic group. All individuals were evaluated in relation to presence of sarcopenia and mTOR signaling pathway. Sarcopenia was evaluated by the combination of low muscle mass and low muscle strength, measured using computerized tomography images, and hand grip strength, respectively. Rectus abdominis muscle biopsy was performed at the time of surgery. mTOR pathway was analyzed by MILLIPLEX Map Kit Phospho/total mTOR 2-Plex Magnetic Bead Panel. Results were presented by phosphor/total mTOR ratio. Independent T test, Kruskal-Wallis test, and Dunn-Bonferroni post hoc were performed for statistical analysis and P < 0.05 was considered. Thirty-six patients and five controls were evaluated. A total of 13 cancer patients (36.1%) had sarcopenia. The phospho/total mTOR ratio was different between the control group (0.167 MFI) and the cancer non-sarcopenic group (0.055 MFI) (P = 0.026) as well as between the control group (0.167 MFI) and the cancer sarcopenic group (0.0049 MFI) (P = 0.041). No difference was observed on the median phospho/total mTOR ratio between the cancer groups (P > 0.05). More research is needed to extrapolate these results.

Conjugated linoleic acid prevents damage caused by intestinal mucositis induced by 5-fluorouracil in an experimental model.

BACKGROUND: Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases. OBJECTIVE: To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model. METHODS: Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated. RESULTS: Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines. CONCLUSION: This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa.

Arginine Supplementation Induces Arginase Activity and Inhibits TNF-α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction.

BACKGROUND: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals. MATERIAL AND METHODS: Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow + IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF-α and IL-10 levels were analyzed in splenic macrophage cultures. RESULTS: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO-/-, and Arg-/- groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF-α levels (Arg vs IO group, P < .05) and maintenance of IL-10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham-/-, IO-/-, and Arg-/- vs other, P < .05). CONCLUSIONS: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF-α levels, which may be directly related to nitric oxide derived from arginine.

Randomized Clinical Trial: Impact of Oral Administration of Saccharomyces boulardii on Gene Expression of Intestinal Cytokines in Patients Undergoing Colon Resection.

BACKGROUND: When intestinal microbiota is imbalanced, a patient becomes more vulnerable to infectious complications; intervention with beneficial probiotics may help lower risk for infection. The aim of this study was to measure levels of inflammatory cytokine messenger RNA (mRNA) in surgical samples of intestinal mucosal tissues from patients who were given the probiotic Saccharomyces boulardii before undergoing colon surgery. METHODS: Thirty-three patients undergoing colon resection were randomly assigned to receive at least 7-day preoperative probiotic treatment (n = 15) or conventional (n = 18) treatment. Probiotic treatment consisted of oral lyophilized S boulardii Cytokine mRNA levels (interleukin [IL]-10, IL-1ß, IL-23A, tumor necrosis factor [TNF]-α, IL-12B, interferon-γ [INF-γ], and IL-17A) were measured in samples obtained during the operation. Postoperative infections were also assessed. RESULTS: Patients who received probiotics had significantly lower mucosal IL-1ß, IL-10, and IL-23A mRNA levels than the control group (P = .001, P = .04, and P = .03, respectively). However, mRNA expression of other cytokines did not differ between the 2 groups (P > .05). The incidence of postoperative infectious complications was 13.3% and 38.8% in probiotic and control groups, respectively (P > .05). There was no perioperative mortality in either group. The mean total length of hospital stay was similar between the groups (P > .05). CONCLUSIONS: Probiotic treatment with S boulardii downregulates both pro- and anti-inflammatory cytokines in the intestinal colonic mucosa with no statistical impact on postoperative infection rates.

Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice.

BACKGROUND: The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. RESULTS: After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p < 0.05) and therefore had a greater weight loss (p < 0.05). The treatment with Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p < 0.05). There were no differences in mucosal lesions, intestinal permeability and sIgA secretion (p > 0.05) in mice pretreated with S. boulardii. CONCLUSIONS: S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil.

Prevalence of pressure ulcers in hospitals in Brazil and association with nutritional status--a multicenter, cross-sectional study.

BACKGROUND: Pressure ulcers (PU) represent a widespread, painful, and expensive health care problem directly associated with increased morbidity, mortality, and length of hospital stay. The aim of this study was to determine the prevalence of PU in hospitalised patients in public and private Brazilian institutions and the ulcers' associations with nutritional status and other risk factors. METHODS: A multicenter, cross-sectional, quantitative and qualitative study was carried out in hospitals in different geographic regions of Brazil from March 2009 to February 2011. The prevalence and characteristics of PU, the nutritional status and the association between the presence of PU, and the nutritional status and other study variables were evaluated. The association of the presence of PU with the study variables was performed by univariate analyses and multivariate logistic regression models. The final multivariate model was one in which all variables were significant at the 0.05 level. RESULTS: According to the subjective global assessment (SGA), the prevalence of PU was 16.9%, and 52.4% of patients were malnourished. PU and their severity were directly associated with malnutrition (P < 0.05). Patients who are bedridden, who are elderly, who have neurological disorders or cancer, who are staying at a public or private institution, and who are staying at the hospital between 8 d and 15 d had an increased risk of PU (P < 0.05). CONCLUSION: The prevalence of PU in Brazilian general hospitals is high, and the prevalence of malnutrition is extremely high. Malnourishment is one of the most important risk factors associated with the development and severity of PU in hospitals. Patients who are malnourished are more prone to developing PU.