Daily Intake of Household-Produced Milk Kefir on Salmonella Typhimurium Infection in C57BL/6 Mice: Mortality, Microbiota Modulation and Immunological Implications.

AIMS: Salmonellosis, a major global cause of diarrheal diseases, significantly impacts the intestinal microbiome. Probiotic-rich beverages, such as kefir, are increasingly utilized as alternative health-promoting beverages associated with various microbiota benefits. This study investigated the repercussions of daily consumption of household-produced milk kefir on Salmonella enterica serovar Typhimurium infection in C57BL-6 mice. METHODS AND RESULTS: Kefir consumption pre infection reduced the presence of inflammatory cells in the colon and altered the cytokine profile by reducing IL-10 and increasing IFN-γ. Despite reducing intestinal inflammation, kefir intake did not yield a prompt response to an acute infection caused by the aggressive pathogen Salmonella. This contributed to increased mortality in the mice, evidenced by higher fecal Salmonella counts post-infection. Metabarcoding analysis demonstrated that the use of kefir before infection increases butyric acid by the higher abundance of Lachnospiraceae and Prevotellaceae families and genus in feces, coupled with an increase in Muribaculaceae family and Bacteroides genus among infected kefir-treated mice. While kefir hinted at microbiota alterations reducing enterobacteria (Helicobacter), decrease IL-10, and increased IFN-γ, butyric acid on pre-infection, the beverage potentially facilitated the systemic translocation of pathogens, intensifying the infection's severity by altering the immune response. CONCLUSIONS: The use of kefir in the dosage of 10% w/v (109 CFU), for acute infections with Salmonella Typhimurium, may not be enough to combat the infection and worsen the prognosis, leaving the intestine less inflamed, favoring the replication and translocation of the pathogen. These findings underscore the importance of prudently evaluating the widespread use of probiotics and probiotic-rich beverages, especially during acute infections, given their potential association with adverse effects during these diseases.

Lactobacillus gasseri LG-G12 Restores Gut Microbiota and Intestinal Health in Obesity Mice on Ceftriaxone Therapy.

Gut microbiota imbalance is associated with the occurrence of metabolic diseases such as obesity. Thus, its modulation is a promising strategy to restore gut microbiota and improve intestinal health in the obese. This paper examines the role of probiotics, antimicrobials, and diet in modulating gut microbiota and improving intestinal health. Accordingly, obesity was induced in C57BL/6J mice, after which they were redistributed and fed with an obesogenic diet (intervention A) or standard AIN-93 diet (intervention B). Concomitantly, all the groups underwent a treatment phase with Lactobacillus gasseri LG-G12, ceftriaxone, or ceftriaxone followed by L. gasseri LG-G12. At the end of the experimental period, the following analysis was conducted: metataxonomic analysis, functional profiling of gut microbiota, intestinal permeability, and caecal concentration of short-chain fatty acids. High-fat diet impaired bacterial diversity/richness, which was counteracted in association with L. gasseri LG-G12 and the AIN-93 diet. Additionally, SCFA-producing bacteria were negatively correlated with high intestinal permeability parameters, which was further confirmed via functional profile prediction of the gut microbiota. A novel perspective on anti-obesity probiotics is presented by these findings based on the improvement of intestinal health irrespective of undergoing antimicrobial therapy or not.

Synbiotic modulates intestinal microbiota metabolic pathways and inhibits DMH-induced colon tumorigenesis through c-myc and PCNA suppression.

The use of probiotic and synbiotic is a promising strategy to modulate the intestinal microbiota, and thereby modify the risk of diseases. In this study, the effect of probiotic VSL#3, isolated or associated with a yacon-based product (PBY), on the functional metabolic pathways of the microbiota, in a colorectal carcinogenesis model, was evaluated. For this, mice induced to carcinogenesis were fed with standard diet AIN-93 M (CON), diet AIN-93 M and VSL#3 (PRO) or diet AIN-93 M with yacon and VSL#3 (SYN). The SYN group showed a highly differentiated intestinal community based on the MetaCyc pathways. Of the 351 predicted functional pathways, 222 differed between groups. Most of them were enriched in the SYN group, namely: amino acid biosynthesis pathways, small molecule biosynthesis pathways (cofactors, prosthetic groups, electron carriers and vitamins) carbohydrate degradation pathways and fermentation pathways. In addition, the synbiotic was able to stimulate the anti-inflammatory immune response and reduce the gene expression of PCNA and c-myc. Thus, we conclude that the synbiotic impacted more significantly the metabolic functions of the microbiota compared to the isolated use of probiotic. We believe that the enrichment of these pathways can exert antiproliferative action, reducing colorectal carcinogenesis. The prediction of the functional activity of the microbiota is a promising tool for understanding the influence of the microbiome on tumor development.

Kefir modulates gut microbiota and reduces DMH-associated colorectal cancer via regulation of intestinal inflammation in adulthood offsprings programmed by neonatal overfeeding.

Obesity is associated with chronic inflammation, intestinal dysbiosis, and colorectal cancer risk. The anti-cancer effects of kefir are highlighted. Here, lactating Wistar rats were divided into: Normal litter (NL); Kefir normal litter (KNL); Small litter (SL); Kefir small litter (KSL). The NL and SL groups received 1 mL of water/day; KNL and KSL received kefir milk daily (108 CFU/mL) during lactation. After weaning, the pups continued to receive the same treatments until 60 days. At 67 days old, colorectal carcinogenesis was induced through intraperitoneal injection of 1,2-dimethylhydrazine. At 240 days, visceral adipose tissue was higher in SL compared to NL, KNL, and KSL. Kefir intake was found to suppress the number of tumors in both KNL and KSL groups (-100% and -71.43%; p < 0.01, respectively). IL-1ß, IL-6, TNF-α, and NO levels in the colon were higher in the NL and SL compared to the KNL and KSL. The gut microbiota in cecal samples of SL was enriched with Alloprevotella, Acinetobacter, and Bacteroides. In contrast, the cecal contents of KSL and KNL were higher Romboutsia. Thus, neonatal overfeeding leads to greater adiposity, inflammation and number of colon tumors in adulthood. Early-life nutrition based on kefir reverted these alterations.

Effect of the ingestion of vegetable oils associated with energy-restricted normofat diet on intestinal microbiota and permeability in overweight women.

Previous studies suggest that the type of dietary fatty acid may modulate the intestinal bacterial ecosystem. However, this effect is still inconclusive. Thus, the aim of this study was to investigate the effect of the intake of vegetable oils rich in different types of fatty acids, associated with energy-restricted normofat diets, on the composition of intestinal microbiota and permeability, on LPS concentrations, and fecal short chain fatty acids and pH. This was a 9 consecutive weeks (±5 days), randomized, parallel, double-blind clinical trial. Overweight women received daily breakfast containing 25 mL of one of the test oils: soybean oil (n = 17), extra virgin olive oil (n = 19) or coconut oil (n = 16). Blood, fecal and urine samples were collected on the first and last day of the experiment for the analysis of the variables of interest. The consumption of the three oils did not affect the diversity and relative abundance of intestinal bacteria. We observed an increase in bacterial richness estimated by the Chao 1 index, and a reduction in the concentration of isovaleric fatty acid in the group that ingested soybean oil. Paracellular and transcellular permeability increased after the ingestion of extra virgin olive oil and coconut oil. However, LPS concentrations remained unchanged. The intake of different types of fatty acids associated with the energy-restricted normofat diet modestly affected the intestinal microbiota and permeability, without resulting in metabolic endotoxemia in overweight women.

Association of Lifestyle and Body Composition on Risk Factors of Cardiometabolic Diseases and Biomarkers in Female Adolescents.

BACKGROUND: Female adolescents are considered a risk group for cardiometabolic disease due to their lifestyle (LS). OBJECTIVE: To evaluate the association between LS classes and body composition groups with cardiometabolic disease risk factors and pro- and anti-inflammatory biomarkers in female adolescents. METHODS: This cross-sectional study was carried out with female adolescents aged 14 to 19 years, from Viçosa-MG, Brazil. Latent class analysis assessed LS classes. Kinanthropometric measurements were taken together with the body fat percentage (BF%), being analyzed by the Dual Energy X-ray Absorptiometry (DEXA) equipment. Blood pressure and biochemical parameters were analyzed in the Health Division of the Federal University of Viçosa. The pro- and anti-inflammatory biomarkers were analyzed using Luminex technology. Associations with biomarkers were estimated by multiple linear regression. RESULTS: 405 female adolescents were evaluated. The majority, 82.57%, 72.90%, and 65.31%, were classified as inactive by the number of steps, with high screen and cell phone time, respectively. Furthermore, 41.55% did meet the minimum of 60 minutes of moderate-to-vigorous physical activity (MVPA) and 54.69% had high values of BF% (DEXA). The "Sedentary & Inactive LS" class together with the high levels of weight and BF% were associated with increased levels of blood pressure, lipid profile, and uric acid. It was also found that "Inactive & Sedentary LS", high BF%, insulin resistance, and ultra-sensitive C-reactive protein were associated with the concentrations of proinflammatory biomarkers of tumor necrosis factor-α, interleukin-6, and leptin. CONCLUSION: We concluded that female adolescents with overweight/obese and high BF% presented higher values of anthropometric indicators, levels of blood pressure, concentration of uric acid and hs-CRP, and lower concentration of HDL. Inactive and Sedentary lifestyle of these girls, along with excess body fat, insulin resistance, and higher concentrations of hs-CRP were associated with the higher concentration proinflammatory markers.

In vitro and in vivo resistance of Lactobacillus rhamnosus GG carried by a mixed pineapple (Ananas comosus L. Merril) and jussara (Euterpe edulis Martius) juice to the gastrointestinal tract.

This study evaluated the viability of Lactobacillus rhamnosus GG (LGG) and its in vitro and in vivo resistance to the gastrointestinal tract (GIT) when carried by a mixed fermented pineapple and jussara juice. The effects of product ingestion on the biochemical characteristics of the blood and on the development of aberrant crypt foci (ACF) in Wistar rats were also determined. The LGG viability in probiotic juice was higher than 7.2 log CFU/mL throughout 28 days at 8 °C. The mean count of the probiotic microorganism in the fecal samples of the rats was 5.6 log CFU/g, identical to the count at the end of the in vitro trial (enteric phase II), indicating that the mixed pineapple and jussara juice was an excellent vehicle for LGG. No difference (p > .05) was verified to ACF among the groups. However, the results for the probiotic culture viability and its in vitro and in vivo resistance to the gastrointestinal tract suggest that this juice is an excellent carrier matrix for LGG and contributed to a reduction in the levels of the LDL (low density lipoprotein) fraction of the blood cholesterol, thus being an aid in the control of coronary diseases.

Abundance of Gut Microbiota, Concentration of Short-Chain Fatty Acids, and Inflammatory Markers Associated with Elevated Body Fat, Overweight, and Obesity in Female Adolescents.

BACKGROUND AND AIMS: Overweight is ever more prevalent in the pediatric population, and this cardiometabolic factor can be associated with inflammatory markers, gut microbiota composition, and short-chain fatty acid (SCFA) concentrations. The aim of this study is to evaluate to what extent the abundance of gut microbiota phyla, SCFA concentrations, and inflammatory markers are associated with elevated body fat percentage (BF%), overweight, and obesity in female adolescents. METHODS: An experimental and comparative study was conducted with 96 girls 14 to 19 years old. They were divided into 3 groups: G1-eutrophic (EUT) and adequate BF%; G2-EUT and high BF%; and G3-overweight (OW) or obese (OB) and high BF%. Waist circumference (WC), waist to height ratio (WtHR), and neck circumference (NC) were analyzed as indicators of central visceral adiposity. The BF% was evaluated by DEXA equipment. A food frequency questionnaire was used to evaluate the main types of food consumed in a week. The abundance of the Firmicutes, Bacteroidetes, and Proteobacteria phyla was measured by real-time polymerase chain reaction (RT-qPCR), and the SFCA concentrations (acetic, butyric, and propionic) were determined by high-performance liquid chromatography (HPLC). The inflammatory markers leptin, tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein (hs-CRP) were assessed. RESULTS: Female adolescents in groups G2 and G3 had greater central visceral adiposity and leptin concentration than those in group G1. No association was found between gut microbiota phyla abundance and SFCA concentrations in any of the groups. WC and frequency of consumption of oily and fatty foods were associated with Firmicutes abundance and SFCA concentrations. Girls with high WC also had the greatest leptin (p < 0.001) and hs-CRP (p = 0.035) concentrations. CONCLUSIONS: Inflammatory markers showed association with increased BMI and high BF% in female adolescents. The abundance of Firmicutes was associated with WC and NC, but not with BMI classification or BF%. Specifically, WC and the consumption of oils and fats showed correlation with SCFA concentrations. Different anthropometric indicators, such as NC and WC, should be incorporated into the clinical evaluation of the nutritional status of individuals in the adolescent population.

High-Fat Diet and Alcohol Intake Promotes Inflammation and Impairs Skin Wound Healing in Wistar Rats.

The wound-healing process is complex and remains a challenging process under the influence of several factors, including eating habits. As improper diets may lead to disorders such as dyslipidemia, insulin resistance, and chronic inflammation, potentially affecting the tissue ability to heal, we decided to investigate the effect of a high-fat diet and alcohol intake on the inflammatory process and skin wound healing in Wistar rats. Male rats (n = 30) were individually housed in cages with food and water ad libitum (registration number 213/2014). After anesthesia, at day 40, three circular wounds (12 mm diameter) were made on the back of each animal, which were then randomly assorted into five treatment groups: C1 (control 1)-water via gavage and standard chow diet; C2 (control 2)-water (no gavage) and standard chow diet; AL (alcohol)-water (no gavage) and alcohol (40%) via gavage and standard chow diet; HF (high fat)-water (no gavage) and high-fat diet (50%); and HF + AL (alcohol/high fat)-water (no gavage), alcohol (40%) via gavage, and high-fat diet. Animals were treated for 61 days. Every seven days, the area and the rate of wound contraction were evaluated. Tissue samples were removed for histopathological analysis and biochemical analyses. Our results showed that wound contraction was not complete in the HF + AL rats. Two specific indices of wound-healing impairment (total cell number and levels of the inflammatory cytokine TGF-ß) were increased in the HF + AL rats. We also observed decreased type I and III collagen fibers in the HF, AL, and HF + AL groups and increased oxidative stress markers in the same groups. We suggest that a high-fat diet combined with alcohol intake contributed to delayed skin wound healing through increase of the inflammatory phase and promoting oxidative stress, which may have led to morphological alterations and impaired matrix remodeling.

The use of antimicrobials as adjuvant therapy for the treatment of obesity and insulin resistance: Effects and associated mechanisms.

The intestinal microbiota has come to be considered an additional risk factor for the development of metabolic diseases. Considering the potential role of antimicrobials as modulators of the intestinal microbiota, they have been investigated for use in the adjuvant treatment of obesity and insulin resistance (IR). In this regard, the present manuscript aimed to review the effect of regular use of antimicrobials on the treatment of obesity and/or IR, as well as its associated mechanisms. The regular use of antimicrobials does not seem to influence the body weight and adiposity of its consumer. Regarding IR, clinical trials did not observe positive effects, on the other hand, most of the experimental studies observed an increase in insulin sensitivity. The mechanisms used by antimicrobials that could lead to the improvement of insulin sensitivity are dependent on the modulation of the intestinal microbiota. This modulation would lead to a reduction in the stimulation of the immune system, as a consequence of improved intestinal barrier and/or the reduction of gram-negative bacteria in the microbiota. In addition, the secretion of glucagon-like peptide-1 would be modulated by metabolites produced by the intestinal microbiota, such as secondary bile acids and short-chain fatty acids. Based on the results obtained to date, more studies should be performed to elucidate the effect of these drugs on obesity and IR, as well as the mechanisms involved. In addition, the cost-benefit of the regular use of antimicrobials should be investigated, as this practice may lead to the development of antimicrobial-resistant microorganisms.

Yacon-Based Product in the Modulation of Intestinal Constipation.

This study aimed to assess the effects of a yacon-based product (YBP) on constipation in adults, including the elderly. Forty-eight individuals were recruited and divided into equal intervention groups named the test and control groups. The YBP (test) and the control (maltodextrin) were dissolved in commercial orange juice. The volunteers for the YBP/test group consumed, on a daily basis, orange juice containing 10 g fructooligosaccharide (FOS)/inulin per day. The control group consumed, on a daily basis, orange juice containing 25 g of maltodextrin. The study had a span of 30 days. We evaluated the participants' frequency of evacuation, consistency of the feces, constipation score, abdominal symptoms (flatulence, pain, and abdominal strain), and effects upon the microbiota, pH, lactate, and short-chain fatty acids (SCFAs) of the feces. The study showed an increased number of evacuations after the consumption of the YBP as well as an improvement in the consistency of the feces and a reduction in the constipation score. After 30 days of intervention, the group that consumed the YBP showed higher counts of Bifidobacterium, lower Clostridium and enterobacteria counts, and lower fecal pH. In relation to SCFAs, no significant change was found after the intervention. However, the lactate concentration was higher in the test group when compared to the post-treatment control group. The YBP was effective in improving constipation symptoms; not only was its functional characteristic in reducing constipation symptoms evident but it also demonstrated usefulness as a potential therapy.

Higher plasma lipopolysaccharide concentrations are associated with less favorable phenotype in overweight/obese men.

PURPOSE: Lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria might be an inflammation trigger in adipose tissue. It has recently been proposed that there is a link between adipose tissue distribution and blood LPS. However, the number of studies on this topic is scarce, and further investigation in humans is required. In this study, we explored the association between plasma LPS concentrations and body fat distribution, as well as the biochemical parameters that may indicate the presence of metabolic disorders. METHODS: Sixty-seven young adult men with body mass index of 26-35 kg/m(2) were evaluated. Anthropometry, body composition and body fat distribution, blood pressure, energy expenditure, physical activity level, dietary intake, and biochemical parameters were assessed. RESULTS: Men with median plasma LPS ≥ 0.9 EU/mL presented higher sagittal abdominal diameter, trunk fat percentage, and android fat percentage, and mass, insulin and alanine aminotransferase concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell dysfunction (HOMA-B) than those with lower plasma LPS. LPS correlated positively with the trunk fat percentage, and android fat percentage, and mass, insulin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase concentrations, as well as HOMA-IR and HOMA-B. CONCLUSION: Our results suggest that a higher plasma LPS concentration is associated with a less favorable phenotype as characterized by higher central adiposity, higher values of HOMA-IR, and beta cell function impairment in overweight/obese men.

Peripheral expression of inflammatory markers in overweight female adolescents and eutrophic female adolescents with a high percentage of body fat.

The objective of this study was to evaluate the peripheral expression of inflammatory markers in adolescents with different nutritional status and its correlation with parameters of the metabolic syndrome. Seventy-two female postpubescent adolescents were divided into 3 groups: eutrophic (Co), eutrophic with a high body fat percentage (HBF), and overweight (OW). Data related to the parameters of the metabolic syndrome and the peripheral expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were evaluated. Higher values of glycemia and insulin resistance were found in the HBF group than in the Co group. No differences related to the peripheral expression of the cytokines were found among the groups. In the HBF group, a positive correlation was observed between TNF-α and IL-6, IL-10 and the proinflammatory cytokines, and IL-6 and glycemia. In the OW group, a positive correlation was found between IL-6 and triglycerides. Adolescents with normal weight but body fat excess present a metabolic profile and body composition similar to those of overweight adolescents. This suggests that these adolescents have a risk of developing cardiovascular diseases similar to that of overweight adolescents. The positive correlation between IL-10 and TNF-α and IL-6 suggests an attempt to inhibit the production of these cytokines by IL-10.