A Mix of Potentially Probiotic Limosilactobacillus fermentum Strains Alters the Gut Microbiota in a Dose- and Sex-Dependent Manner in Wistar Rats.

Multi-strain Limosilactobacillus (L.) fermentum is a potential probiotic with reported immunomodulatory properties. This study aimed to evaluate the composition, richness, and diversity of the gut microbiota in male and female rats after treatment with a multi-strain of L. fermentum at different doses. Thirty rats (fifteen male and fifteen female) were allocated into a control group (CTL), a group receiving L. fermentum at a dose of 108 CFU (Lf-108), and a group receiving L. fermentum at a dose of 1010 CFU (Lf-1010) for 13 weeks. Gut microbiota and serum cytokine levels were evaluated after L. fermentum treatment. Male CTL rats had a lower relative abundance of Bifidobacteriaceae and Prevotella and a lower alpha diversity than their female CTL counterparts (p < 0.05). In addition, male CTL rats had a higher Firmicutes/Bacteroidetes (F/B) ratio than female CTL rats (p < 0.05). In female rats, the administration of L. fermentum at 108 CFU decreased the relative abundance of Bifidobacteriaceae and Anaerobiospirillum and increased Lactobacillus (p < 0.05). In male rats, the administration of L. fermentum at 1010 CFU decreased the F/B ratio and increased Lachnospiraceae and the diversity of the gut microbiota (p < 0.05). The relative abundance of Lachnospiraceae and the alpha-diversity of gut microbiota were negatively correlated with serum levels of IL1ß (r = -0.44) and TNFα (r = -0.39), respectively. This study identified important changes in gut microbiota between male and female rats and showed that a lower dose of L. fermentum may have more beneficial effects on gut microbiota in females, while a higher dose may result in more beneficial effects on gut microbiota in male rats.

Limosilactobacillus fermentum Strains as Novel Probiotic Candidates to Promote Host Health Benefits and Development of Biotherapeutics: A Comprehensive Review.

Fruits and their processing by-products are sources of potentially probiotic strains. Limosilactobacillus (L.) fermentum strains isolated from fruit processing by-products have shown probiotic-related properties. This review presents and discusses the results of the available studies that evaluated the probiotic properties of L. fermentum in promoting host health benefits, their application by the food industry, and the development of biotherapeutics. The results showed that administration of L. fermentum for 4 to 8 weeks promoted host health benefits in rats, including the modulation of gut microbiota, improvement of metabolic parameters, and antihypertensive, antioxidant, and anti-inflammatory effects. The results also showed the relevance of L. fermentum strains for application in the food industry and for the formulation of novel biotherapeutics, especially nutraceuticals. This review provides evidence that L. fermentum strains isolated from fruit processing by-products have great potential for promoting host health and indicate the need for a translational approach to confirm their effects in humans using randomized, double-blind, placebo-controlled trials.

Safety Evaluation of a Novel Potentially Probiotic Limosilactobacillus fermentum in Rats.

Limosilactobacillus (L) fermentum (strains 139, 263, 296) is a novel probiotic mixture isolated from fruit processing by-products. The use of this formulation has been associated with improvements in cardiometabolic, inflammatory, and oxidative stress parameters. The present study evaluated the safety of a potential multi-strain probiotic by genotoxicity (micronucleus assay) and subchronic toxicity study (13-week repeated dose). In the genotoxicity evaluation, L. fermentum 139, 263, 296 did not increase the frequency of micronuclei in erythrocytes of rats of both sexes at doses up to 1010 CFU/mL. In the subchronic toxicity study, the administration of L. fermentum did not promote adverse health effects, such as behavioral changes, appearance of tumors, changes in hematological and biochemical parameters. In addition, higher doses of L. fermentum 139, 263, 296 have been shown to reduce the levels of pro-inflammatory cytokines. Administration of potentially probiotic L. fermentum did not promote adverse health effects in rats and could be evaluated as a potential probiotic for humans.

Limosilactobacillus fermentum Strains with Claimed Probiotic Properties Exert Anti-oxidant and Anti-inflammatory Properties and Prevent Cardiometabolic Disorder in Female Rats Fed a High-Fat Diet.

This study assessed the effects of a mixed formulation containing Limosilactobacillus (L.) fermentum 139, L. fermentum 263, and L. fermentum 296 on cardiometabolic parameters, inflammatory markers, short-chain fatty acid (SCFA) fecal contents, and oxidative stress in colon, liver, heart, and kidney tissues of female rats fed a high-fat diet (HFD). Female Wistar rats were allocated into control diet (CTL, n = 6), HFD (n = 6), and HFD receiving L. fermentum formulation (HFD-LF, n = 6). L. fermentum formulation (1 × 109 CFU/mL of each strain) was administered two twice a day for 4 weeks. Administration of L. fermentum increased acetate and succinate fecal contents and reduced hyperlipidemia and hyperglycemia in rats fed a HFD (p < 0.05). Administration of L. fermentum decreased low-grade inflammation and improved antioxidant capacity along the gut, liver, heart, and kidney tissues in female rats fed a HFD (p < 0.05). Administration of L. fermentum prevented dyslipidemia, inflammation, and oxidative stress in colon, liver, heart, and kidney in female rats fed a HFD.

Limosilactobacillus fermentum prevents gut-kidney oxidative damage and the rise in blood pressure in male rat offspring exposed to a maternal high-fat diet.

Oxidative stress along the gut-kidney axis is a risk factor for developing arterial hypertension in offspring from dams fed a high-fat diet. Considering the antioxidant capacity of probiotic strains, this study evaluated the effects of a daily multistrain formulation with Limosilactobacillus fermentum 139, 263, and 296 on blood pressure (BP), renal function, and oxidative stress and along the gut-kidney axis in male offspring from dams fed a high-fat high-cholesterol (HFHC) diet during pregnancy and lactation. Dams were fed a diet control or HFHC diet during pregnancy and lactation. At 100 days of age, part of the male offspring from dams fed a HFHC diet received Limosilactobacillus fermentum formulation for 4 weeks (HFHC + Lf) daily. After the 4-week intervention, BP (tail-cuff plethysmography) and urinary and biochemical variables were measured. In addition, malondialdehyde levels, enzymatic activities of superoxide dismutase, catalase, glutathione-S-transferase, and nonenzymatic antioxidant defense (thiols content) were measured in the colon and renal cortex. Male offspring from dams fed a HFHC had increased blood pressure, impaired renal function, and oxidative stress along the gut-kidney axis. Administration of Limosilactobacillus fermentum reduced systolic, diastolic, and mean blood pressure levels and alleviated renal function impairment and oxidative stress along the gut-kidney axis in male offspring from dams fed a HFHC diet. Administration of Limosilactobacillus fermentum formulation attenuated programmed hypertension in the HFHC group through oxidative stress modulation along the gut-kidney axis.

Effects of a Mixed Limosilactobacillus fermentum Formulation with Claimed Probiotic Properties on Cardiometabolic Variables, Biomarkers of Inflammation and Oxidative Stress in Male Rats Fed a High-Fat Diet.

High-fat diet (HFD) consumption has been linked to dyslipidemia, low-grade inflammation and oxidative stress. This study investigated the effects of a mixed formulation with Limosilactobacillusfermentum 139, L. fermentum 263 and L. fermentum 296 on cardiometabolic parameters, fecal short-chain fatty acid (SCFA) contents and biomarkers of inflammation and oxidative stress in colon and heart tissues of male rats fed an HFD. Male Wistar rats were grouped into control diet (CTL, n = 6), HFD (n = 6) and HFD with L. fermentum formulation (HFD-Lf, n = 6) groups. The L.fermentum formulation (1 × 109 CFU/mL of each strain) was administered twice a day for 4 weeks. After a 4-week follow-up, biochemical parameters, fecal SCFA, cytokines and oxidative stress variables were evaluated. HFD consumption caused hyperlipidemia, hyperglycemia, low-grade inflammation, reduced fecal acetate and propionate contents and increased biomarkers of oxidative stress in colon and heart tissues when compared to the CTL group. Rats receiving the L. fermentum formulation had reduced hyperlipidemia and hyperglycemia, but similar SCFA contents in comparison with the HFD group (p < 0.05). Rats receiving the L. fermentum formulation had increased antioxidant capacity throughout the colon and heart tissues when compared with the control group. Administration of a mixed L. fermentum formulation prevented hyperlipidemia, inflammation and oxidative stress in colon and heart tissues induced by HFD consumption.

Food addiction symptoms and metabolic changes in children and adolescents with the double burden of malnutrition.

The double burden of malnutrition (DBM) has been described in many low-/middle-income countries. We investigated food addiction, thyroid hormones, leptin, the lipid/glucose profile and body composition in DBM children/adolescents. Subjects were allocated into groups according to nutritional status: control (C, n 28), weight excess (WE, n 23) and DBM (WE plus mild stunting, n 22). Both the DBM and WE groups showed higher mean insulin concentrations than the control (DBM = 57·95 (95 % CI 47·88, 70·14) pmol/l, WE = 74·41 (95 % CI 61·72, 89·80) pmol/l, C = 40·03 (95 % CI 34·04, 47·83) pmol/l, P < 0·001). WE and DBM showed more food addiction symptoms than the control (3·11 (95 % CI 2·33, 3·89), 3·41 (95 % CI 2·61, 4·20) and 1·66 (95 % CI 0·95, 2·37)). In DBM individuals, addiction symptoms were correlated with higher body fat and higher insulin and leptin levels. These data provide preliminary evidence consistent with the suggestion that DBM individuals have a persistent desire to eat, but further studies are required to confirm these results in a larger study. These hormonal changes and high body fat contribute to the development of diabetes in long term.

Effects of probiotic therapy on cardio-metabolic parameters and autonomic modulation in hypertensive women: a randomized, triple-blind, placebo-controlled trial.

BACKGROUND AND AIMS: We assessed the effects of probiotic therapy for 8 weeks on cardiometabolic variables and autonomic function in women medically diagnosed with arterial hypertension. METHODS AND RESULTS: Forty women with arterial hypertension, 20-50 years, were assigned to two groups in this randomized, triple-blind, placebo-controlled clinical trial. Patients in the probiotic group received a daily sachet containing Lactobacillus para casei LPC-37, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM, and Bifidobacterium lactis HN019 (109 CFU of each strain) for 8 weeks. Patients in the placebo group received identical sachets with polydextrose (1 g day-1, for 8 weeks). Anthropometric, BP, electrocardiogram, biochemical measurements, fecal microbiota composition, and glucose hydrogen breath test were assessed at baseline and after 8 weeks intervention. Anthropometric variables (weight, BMI, and waist circumference) were similar between the two groups (p > 0.05). Probiotic supplementation significantly reduced fasting glucose (change -10.3 mg dL-1, p < 0.05) and cholesterol levels (change -23.6 mg dL-1, p < 0.05), and increased the HDL-cholesterol (change 6.5 mg dL-1, p < 0.05) compared with the baseline condition. Probiotic supplementation lowered, although without statistical significance, systolic BP by about 5 mmHg and diastolic BP by about 2 mmHg in hypertensive women. Lastly, probiotic administration reduced the low frequency (LF) oscillation and LF/high frequency (HF) ratio (p < 0.05) in the frequency domain of heart rate variability, suggesting an improvement in autonomic modulation. CONCLUSION: Probiotic therapy for 8 weeks reduced fasting glucose levels, and improved the lipid profile and autonomic modulation in hypertensive women.

Short- and long-term effects of maternal dyslipidaemia on blood pressure and baroreflex sensitivity in male rat offspring.

Maternal dyslipidaemia is a predisposing factor for arterial hypertension in male rat offspring at adulthood. This study was designed to investigate the short- and long-term effects of maternal dyslipidaemia on blood pressure (BP) and baroreflex control in male rat offspring. Animals were obtained from mothers who received a dyslipidaemic (DLP, n = 7) or control (CTL, n = 7) diet during pregnancy and lactation. At 30 and 90 days of age, arterial pressure (AP), heart rate (HR) and baroreflex function were evaluated. In addition, spectral analysis of the systolic AP, diastolic AP, mean AP, HR, and spontaneous baroreflex were assessed. Data were expressed as mean ± SEM and Student's t-test was used for comparison among groups, with statistical significance considered to be P < .05. At 30 days of age, male offspring had similar BP, HR and preserved baroreflex sensitivity. In addition, low frequency (LF) oscillation, high frequency (HF) oscillation and LF/HF ratio of AP and HR were similar in juvenile rats. At 90 days of age, male offspring from dyslipidaemic dams had augmented BP (P < .05) when compared to CTL group. Adult male rats from dyslipidaemic dams had a reduction in baroreflex control (P < .05) in comparison to CTL rats. The present study indicates that offspring from dams fed on a dyslipidaemic diet during pregnancy and lactation do not show alteration in blood pressure and baroreflex control in early life, but display a decline in baroreflex control and hypertension in adulthood.

Saline extract of Pilosocereus gounellei stem has antinociceptive effect in mice without showing acute toxicity and altering motor coordination.

People broadly use medicinal plants although their safety and efficacy are often neglected. Several Cactaceae plants are used for medicinal purposes, but Pilosocereus gounellei (xique-xique) has been little studied for their pharmacological properties. In this study, a saline extract from Pilosocereus gounellei stem was evaluated for acute toxicity, effects on motor function, and antinociceptive activity in mice. Thin-layer chromatography and high-performance liquid chromatography revealed the presence of flavonoids and reducing sugars. No death of mice was noted with oral treatments at 2000 and 5000 mg/kg. Body weight gain, food intake, and water consumption were not affected with treatment at 2000 mg/kg. The number of segmented leukocytes was higher in the treated mice than in control, and reduced serum levels of cholesterol and triglycerides were detected after both extract treatments. No histological alterations in the liver, heart, lung, kidney, and spleen were detected. Open field and rotarod tests showed that the extract did not affect motor function and exploratory activity. Antinociceptive activity was detected in acetic acid-induced writhing, tail-immersion, and formalin tests, indicating interference with both non-inflammatory and inflammatory pain. In conclusion, the P. gounellei extract has antinociceptive activity in mice without showing toxicity and altering motor coordination.