Preclinical and clinical relevance of probiotics and synbiotics in colorectal carcinogenesis: a systematic review.

CONTEXT: Recent evidence suggests that modulation of the gut microbiota may help prevent colorectal cancer. OBJECTIVE: The aim of this systematic review was to investigate the role of probiotics and synbiotics in the prevention of colorectal cancer and to clarify potential mechanisms involved. DATA SOURCES: The PubMed, ScienceDirect, and LILACS databases were searched for studies conducted in humans or animal models and published up to August 15, 2018. STUDY SELECTION: Clinical trials and placebo-controlled experimental studies that evaluated the effects of probiotics and synbiotics in colorectal cancer and cancer associated with inflammatory bowel disease were included. Of 247 articles identified, 31 remained after exclusion criteria were applied. A search of reference lists identified 5 additional studies, for a total of 36 included studies. DATA EXTRACTION: Two authors independently assessed risk of bias of included studies and extracted data. Data were pooled by type of study, ie, preclinical or clinical. RESULTS: The results showed positive effects of probiotics and synbiotics in preventing colorectal cancer. The main mechanisms identified were alterations in the composition and metabolic activity of the intestinal microbiota; reduction of inflammation; induction of apoptosis and inhibition of tumor growth; modulation of immune responses and cell proliferation; enhanced function of the intestinal barrier; production of compounds with anticarcinogenic activity; and modulation of oxidative stress. CONCLUSIONS: Probiotics or synbiotics may help prevent colorectal cancer, but additional studies in humans are required to better inform clinical practice.

Trypanosoma cruzi infection induces morphological reorganization of the myocardium parenchyma and stroma, and modifies the mechanical properties of atrial and ventricular cardiomyocytes in rats.

BACKGROUND: This study investigates morphofunctional adaptations of the heart stroma and parenchyma in rats that are chronically infected with Trypanosoma cruzi. METHODS: Four-month-old male Wistar rats were randomized into control (n=14) and infected (n=14) groups. Infected animals were inoculated with T. cruzi Y strain. After 9 weeks, the animals were euthanized, and the right atrium (RA) and left ventricle (LV) were removed for biochemical, stereological, and cardiomyocyte mechanical analyses. RESULTS: Infected animals presented cardiomyocyte atrophy and myocardial fibrosis. For these animals, the total volume, length, surface area, and cross-sectional area of cardiomyocytes were significantly reduced, and the total interstitial and collagen volumes were significantly increased in the RA and LV compared to the controls. The total volume and length of blood vessels were significantly increased in the LV, and the total blood vessel surface area was significantly higher in the RA of infected animals. RA and LV cardiomyocytes from infected animals exhibited a significant reduction in cell shortening (43.02% and 24.98%, respectively), prolongation of the time to the peak of contraction (17.09%) and the time to half relaxation (23.68%) compared to non-infected animals. Lipid hydroperoxides, but not mineral concentrations, were significantly increased in the RA and LV from infected animals, showing an inverse correlation with cell shortening. CONCLUSIONS: T. cruzi infection induces global structural remodeling of the RA and LV in rats. This remodeling coexists with cardiomyocyte contractility dysfunction, which is possibly related to the abnormal organization of the myocardial stroma and increased cellular lipid peroxidation.

Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors.

SCFA provide energy to the host and influence lipid and glucose metabolism, suggesting that they may have an impact on the occurrence of metabolic risk factors. The aim of the present study was to determine the concentration of SCFA in faeces of lean and obese individuals and to analyse whether associations between faecal SCFA and metabolic syndrome parameters are present. Lean (n 20) and obese (n 20) women of similar age (28·5 (sd 7·6) v. 30·7 (sd 6·5) years, P= 0·33) participated in the study. Anthropometric measurements, body composition, blood pressure and biochemical parameters were assessed. SCFA were extracted from faeces and quantified by GC. Blood pressure and blood glucose, although within the normal limits, were higher in the obese group compared to lean subjects (P< 0·05). Lower HDL concentration and higher insulin and homeostasis model assessment (HOMA) index were observed in the obese than in the lean group (P< 0·05). The median values of SCFA (% w/w) from the lean and obese groups were butyric (0·021 v. 0·044, P= 0·024), propionic (0·021 v. 0·051, P= 0·007) and acetic (0·03 v. 0·061, P= 0·01). SCFA correlated positively with metabolic syndrome risk factors such as adiposity, waist circumference and HOMA index (P< 0·05), and inversely with HDL (P< 0·05). Our results suggest that the higher faecal concentration of SCFA is associated with metabolic risk factors and thus may influence metabolic homeostasis.

Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.

Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-ß, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

Monocyte chemoattractant protein-1 involvement in the alpha-tocopherol-induced reduction of atherosclerotic lesions in apolipoprotein E knockout mice.

We studied the effects of alpha-tocopheryl acetate supplementation on the development of fatty streaks and its ability to modulate the expression of monocyte chemoattractant protein (MCP)-1 in aortic lesions of apolipoprotein E knockout mice. For this purpose, 16-week-old apolipoprotein E knockout mice received alpha-tocopherol supplementation (800 mg)/kg diet) for 6 weeks. After this time, total and lipoprotein cholesterol in the serum, hepatic tocopherol, aortic lesion area and MCP-1 (protein and mRNA) expression were analysed. Our present results showed that the dietary supplementation with alpha-tocopherol did not reduce serum cholesterol nor change lipoprotein profile, but it reduced the area of the aortic lesion by 55 %. The reduction in the lesion size was correlated with the reduced expression of MCP-1 mRNA and protein, as detected by real-time quantitative polymerase chain reaction and immunohistochemistry respectively. In conclusion, the results obtained here are relevant to the study of atherosclerosis, as they correlate the effectiveness of vitamin E supplementation in inhibiting the plaque formation with diminished expression of MCP-1 at the aortic lesion.