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.

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.

Targeting Gut Microbiota with Probiotics and Phenolic Compounds in the Treatment of Atherosclerosis: A Comprehensive Review.

Atherosclerosis (AS) is a chronic inflammatory vascular disease. Dysregulated lipid metabolism, oxidative stress, and inflammation are the major mechanisms implicated in the development of AS. In addition, evidence suggests that gut dysbiosis plays an important role in atherogenesis, and modulation of the gut microbiota with probiotics and phenolic compounds has emerged as a promising strategy for preventing and treating AS. It has been shown that probiotics and phenolic compounds can improve atherosclerosis-related parameters by improving lipid profile, oxidative stress, and inflammation. In addition, these compounds may modulate the diversity and composition of the gut microbiota and improve atherosclerosis. The studies evaluated in the present review showed that probiotics and phenolic compounds, when consumed individually, improved atherosclerosis by modulating the gut microbiota in various ways, such as decreasing gut permeability, decreasing TMAO and LPS levels, altering alpha and beta diversity, and increasing fecal bile acid loss. However, no study was found that evaluated the combined use of probiotics and phenolic compounds to improve atherosclerosis. The available literature highlights the synergistic potential between phenolic compounds and probiotics to improve their health-promoting properties and functionalities. This review aims to summarize the available evidence on the individual effects of probiotics and phenolic compounds on AS, while providing insights into the potential benefits of nutraceutical approaches using probiotic strains, quercetin, and resveratrol as potential adjuvant therapies for AS treatment through modulation of the gut microbiota.

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.

Potential role of Limosilactobacillus fermentum as a probiotic with anti-diabetic properties: A review.

Oxidative stress, inflammation, and gut microbiota impairments have been implicated in the development and maintenance of diabetes mellitus. Strategies capable of recovering the community of commensal gut microbiota and controlling diabetes mellitus have increased in recent years. Some lactobacilli strains have an antioxidant and anti-inflammatory system capable of protecting against oxidative stress, inflammation, and diabetes mellitus. Experimental studies and some clinical trials have demonstrated that Limosilactobacillus fermentum strains can beneficially modulate the host antioxidant and anti-inflammatory system, resulting in the amelioration of glucose homeostasis in diabetic conditions. This review presents and discusses the currently available studies on the identification of Limosilactobacillus fermentum strains with anti-diabetic properties, their sources, range of dosage, and the intervention time in experiments with animals and clinical trials. This review strives to serve as a relevant and well-cataloged reference of Limosilactobacillus fermentum strains capable of inducing anti-diabetic effects and promoting health benefits.

Evidence for Quercetin as a Dietary Supplement for the Treatment of Cardio-Metabolic Diseases in Pregnancy: A Review in Rodent Models.

Quercetin supplementation during pregnancy and lactation has been linked to a lower risk of maternal cardio-metabolic disorders such as gestational diabetes mellitus (GDM), dyslipidemia, preeclampsia, attenuation of malnutrition-related conditions, and gestational obesity in animal studies. Pre-clinical studies have shown that maternal supplementation with quercetin reduces cardio-metabolic diseases in dams and rodents' offspring, emphasizing its role in modifying phenotypic plasticity. In this sense, it could be inferred that quercetin administration during pregnancy and lactation is a viable strategy for changing cardio-metabolic parameters throughout life. Epigenetic mechanisms affecting the AMP-activated protein kinase (AMPK), nuclear factor-kappa B (NF-κB), and phosphoinositide 3-kinase (PI3 K) pathways could be associated with these changes. To highlight these discoveries, this review outlines the understanding from animal studies investigations about quercetin supplementation and its capacity to prevent or decrease maternal and offspring cardio-metabolic illnesses and associated comorbidities.