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.

Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1ß) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

Determining the minimum ripening time of artisanal Minas cheese, a traditional Brazilian cheese.

Physical, physicochemical, and microbiological changes were monitored in 256 samples of artisanal Minas cheese from eight producers from Serro region (Minas Gerais, Brazil) for 64 days of ripening to determine the minimum ripening time for the cheese to reach the safe microbiological limits established by Brazilian legislation. The cheeses were produced between dry season (April-September) and rainy season (October-March); 128 cheeses were ripened at room temperature (25 ± 4 °C), and 128 were ripened under refrigeration (8 ± 1 °C), as a control. No Listeria monocytogenes was found, but one cheese under refrigeration had Salmonella at first 15 days of ripening. However, after 22 days, the pathogen was not detected. Seventeen days was the minimum ripening time at room temperature to reduce at safe limits of total coliforms > 1000 cfu.g (-1) ), Escherichia coli and Staphylococcus aureus (> 100 cfu.g (-1) ) in both periods of manufacture. Otherwise under refrigeration, as expected, the minimum ripening time was longer, 33 days in the dry season and 63 days in the rainy season. To sum up, we suggest that the ripening of artisanal Minas cheese be done at room temperature, since this condition shortens the time needed to reach the microbiological quality that falls within the safety parameters required by Brazilian law, and at the same time maintain the appearance and flavor characteristics of this traditional cheese.

Determining the minimum ripening time of artisanal Minas cheese, a traditional Brazilian cheese

Physical, physicochemical, and microbiological changes were monitored in 256 samples of artisanal Minas cheese from eight producers from Serro region (Minas Gerais, Brazil) for 64 days of ripening to determine the minimum ripening time for the cheese to reach the safe microbiological limits established by Brazilian legislation. The cheeses were produced between dry season (April–September) and rainy season (October–March); 128 cheeses were ripened at room temperature (25 ± 4 °C), and 128 were ripened under refrigeration (8 ± 1 °C), as a control. No Listeria monocytogenes was found, but one cheese under refrigeration had Salmonella at first 15 days of ripening. However, after 22 days, the pathogen was not detected. Seventeen days was the minimum ripening time at room temperature to reduce at safe limits of total coliforms > 1000 cfu.g−1), Escherichia coli and Staphylococcus aureus (> 100 cfu.g−1) in both periods of manufacture. Otherwise under refrigeration, as expected, the minimum ripening time was longer, 33 days in the dry season and 63 days in the rainy season. To sum up, we suggest that the ripening of artisanal Minas cheese be done at room temperature, since this condition shortens the time needed to reach the microbiological quality that falls within the safety parameters required by Brazilian law, and at the same time maintain the appearance and flavor characteristics of this traditional cheese.

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.

Potential mechanisms for the emerging link between obesity and increased intestinal permeability.

Recently, increased attention has been paid to the link between gut microbial composition and obesity. Gut microbiota is a source of endotoxins whose increase in plasma is related to obesity and insulin resistance through increased intestinal permeability in animal models; however, this relationship still needs to be confirmed in humans. That intestinal permeability is subject to change and that it might be the interface between gut microbiota and endotoxins in the core of metabolic dysfunctions reinforce the need to understand the mechanisms involved in these aspects to direct more efficient therapeutic approaches. Therefore, in this review, we focus on the emerging link between obesity and increased intestinal permeability, including the possible factors that contribute to increased intestinal permeability in obese subjects. We address the concept of intestinal permeability, how it is measured, and the intestinal segments that may be affected. We then describe 3 factors that may have an influence on intestinal permeability in obesity: microbial dysbiosis, dietary pattern (high-fructose and high-fat diet), and nutritional deficiencies. Gaps in the current knowledge of the role of Toll-like receptors ligands to induce insulin resistance, the routes for lipopolysaccharide circulation, and the impact of altered intestinal microbiota in obesity, as well as the limitations of current permeability tests and other potential useful markers, are discussed. More studies are needed to reveal how changes occur in the microbiota. The factors such as changes in the dietary pattern and the improvement of nutritional deficiencies appear to influence intestinal permeability, and impact metabolism must be examined. Also, additional studies are necessary to better understand how probiotic supplements, prebiotics, and micronutrients can improve stress-induced gastrointestinal barrier dysfunction and the influence these factors have on host defense. Hence, the topics presented in this review may be beneficial in directing future studies that assess gut barrier function in obesity.

Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors.

BACKGROUND & AIMS: Altered intestinal permeability has been shown to be associated with metabolic alterations in animal models of obesity, but not in humans. The aim of this study was to assess intestinal permeability in obese women and verify if there is any association with anthropometric measurements, body composition or biochemical variables. METHODS: Twenty lean and twenty obese females participated in the study. Anthropometric measurements, body composition and blood pressure were assessed and biochemical analyses were performed. Administration of lactulose and mannitol followed by their quantification in urine was used to assess the intestinal permeability of volunteers. RESULTS: The obese group showed lower HDL (p < 0.05), higher fasting glucose, insulin, HOMA index and lactulose excretion than the lean group (p < 0.05), suggesting increased paracellular permeability. Lactulose excretion showed positive correlation (p < 0.05) with waist and abdominal circumference. Blood insulin and the HOMA index also increased with the increase in mannitol and lactulose excretion and in the L/M ratio (p < 0.05). L/M ratio presented a negative correlation with HDL concentration (p < 0.05). CONCLUSIONS: We demonstrated that intestinal permeability parameters in obese women are positively correlated with anthropometric measurements and metabolic variables. Therapeutic interventions focused on intestine health and the modulation of intestinal permeability should be explored in the context of obesity.

Growth of preschool children was improved when fed an iron-fortified fermented milk beverage supplemented with Lactobacillus acidophilus.

Food fortification is an efficient strategy applied to overcome iron deficiency anemia. This study investigated the effect of iron fortification with probiotic bacteria in a milk beverage on growth and iron status of preschool children with a usually low-bioavailable-iron diet intake. The fermented milk beverage was fortified with iron amino acid chelate (3 mg iron per 80 mL) and supplemented with Lactobacillus acidophilus (test) or not (control). The beverage was fed to 190 children aged 2 to 5 years for a duration of 101 days. Anthropometric, hematologic, and nutritional assessments were carried out before and after the intervention. The levels of red blood cells, hemoglobin, and hematocrit decreased (P < .001) in both groups (test and control) but remained within the reference range. The children fed the probiotic milk beverage exhibited higher red blood cell status and a positive correlation between iron intake and hemoglobin. An increased serum ferritin level was observed in the control group (P < .001). Nutritional status was improved after intervention in both groups by comparing the indices of weight for age and height for age. However, no difference was observed in the weight for height index in these groups. Energy and nutrient intake increased (P < .001) with intervention, and the prevalence of inadequacy was reduced. The fortified beverage contributed to improved nutrient intake and nutritional status of the preschool children. The higher demand and mobilization of nutrients to offset growth may have contributed to maintain blood parameters at borderline levels.