Western dietary patterns are major drivers of cardiometabolic dysfunction, partly mediated by gut microbiome dysbiosis and sustained inflammation along the gut–brain axis. In this study, we investigated whether a synbiotic formulation combining Limosilactobacillus (L.) fermentum strains with polyphenols, quercetin, and resveratrol could mitigate cardiovascular and neuroinflammatory alterations induced by a Western diet. Male Wistar rats were assigned to three groups receiving a standard diet, a Western diet, or a Western diet supplemented with the synbiotic. Arterial pressure and cardiac autonomic function were assessed, alongside gut microbiome diversity and composition, and gene expression analyses of intestinal permeability and inflammatory markers in colonic tissue and in the brainstem. Synbiotic supplementation prevented the Western diet–induced cardiac autonomic imbalance. These functional benefits were accompanied by marked modulation of the gut microbiome, characterized by increased abundance of beneficial bacterial taxa (Gemmiger formicilis, Lactobacillus acidophilus, Flavonifractor plautii, Blautia glucerasea, Blautia stercoris, Roseburia faecis, Marvinbryantia formatexigens, and Romboutsia timonensis) and significant shifts in microbial community structure. In parallel, synbiotic supplementation attenuated pro-inflammatory gene expression in both peripheral and central tissues associated with the gut–brain axis (Nlrp3, Casp1, Il-1β). These findings demonstrate that synbiotic supplementation exerts integrated anti-inflammatory and neuroautonomic protective effects through the gut–brain axis. Our results support the therapeutic potential of combined probiotic–phenolic strategies to counteract cardiometabolic dysfunction induced by Western diets.

Plant-based proteins are promising alternatives to animal proteins for supporting muscle synthesis and preventing sarcopenia. This study examined whether protein digestates (PDs) from pea and fava bean isolates modulate intestinal Fibroblast Growth Factor 19 (FGF19), a hormone central to energy and muscle mass regulation. Human HT29 cells were exposed to PDs, GW4064 (FXR agonist), or rosiglitazone (PPAR gamma agonist). FGF19 secretion was assessed by ELISA, gene expression by RT-qPCR, and FXR protein by Western-blot. At 6 h, PDs alone had no effect on FGF19 expression but potentiated GW4064 activity by lowering its EC50. At 24 h, PDs modestly increased FGF19 and continued to potentiate GW4064 activity. Rosiglitazone + GW4064 markedly increased FGF19 and FXR expression, an effect abolished by GW9662 (PPAR gamma inhibitor), confirming PPAR gamma involvement. GW9662 also suppressed FGF19 induction by PDs + GW4064. Thus, PPAR gamma may regulate the FXR-FGF19 axis in enterocytes. Both PDs and rosiglitazone enhance FXR-mediated FGF19, with PDs partly acting through PPAR gamma. Pea and fava bean proteins may offer nutritional strategies for metabolic health and sarcopenia prevention.

Low-protein diets (LPD) are recommended in chronic kidney disease (CKD) to reduce disease progression. However, their clinical efficacy and safety are debated due to the risk of protein-energy wasting. A deeper mechanistic understanding is therefore required. Herein, the metabolic effects of LPD in both murine models and a randomized controlled trial in nondiabetic CKD patients were investigated, focusing on glucose homeostasis, plasmatic uremic toxin (UTs) levels, gut microbiota remodeling, and endocrine adaptations. In both experimental and clinical settings, LPD improved glucose tolerance and significantly decreased circulating levels of gut-derived UTs while reducing body weight (-33% weight gain in mice and a decrease in body mass index of ~-0.5 kg/m2 in humans). These metabolic improvements were associated with alterations in gut microbiota composition and function, including the downregulation of microbial pathways involved in aromatic amino acid biosynthesis. In both mice and patients, LPD triggered a significant hepatic induction of fibroblast growth factor 21 (FGF21), an endocrine regulator of amino acid deficiency (+2.9-fold in human and 28-fold in mice) FGF21 levels correlated negatively with lean mass and positively with fat mass and glycemic control, supporting a dual role in metabolic adaptation and catabolic signaling. To mitigate the adverse nutritional effects of LPD, we administered Lactiplantibacillus plantarum WJL (LpWJL), a probiotic previously found to enhance growth of under nutritional stress in CKD mice. LpWJL restored circulating amino acid levels, suppressed FGF21 induction (-26%) and stress-related biosynthetic responses, and preserved body weight (+247% weight gain) and composition, without impairing the benefits of LPD on kidney and metabolic parameters. The present findings identify UTs and FGF21 as crucial factors of the metabolic response to LPD, and support microbiota-targeted strategies, such as LpWJL supplementation, to enhance LPD efficacy. Clinical trials are, however, required to confirm their relevance in CKD management.

Chronic kidney disease (CKD) is often associated with increased intestinal permeability, commonly referred to as "leaky gut." This study aimed to investigate how uremic conditions affect gut barrier integrity using in vitro, ex vivo, and in vivo models. Caco-2 cells exposed to plasma from hemodialysis (HD) patients exhibited increased permeability. HD plasma selectively upregulated claudin-1 expression at both mRNA and protein levels, without affecting ZO-1 or occludin. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate did not replicate these effects. CKD mice showed enhanced paracellular intestinal permeability, confirmed by elevated plasma levels of LBP and FD4, both in vivo and ex vivo. Claudin-1 overexpression was also observed in the colons of CKD mice. In addition, CKD mice displayed increased cecal ammonia concentrations. Exposure to ammonia, both in vitro and ex vivo, significantly disrupted epithelial barrier integrity and increased colonic permeability, supporting the hypothesis that bacterial urease activity and ammonia production contribute to gut barrier dysfunction in CKD. These findings reveal a potential mechanistic link between renal failure, luminal ammonia, and "leaky gut."

Childhood obesity is associated with gut microbiome dysbiosis, inflammation, and early cardiac autonomic dysfunction. Lifestyle interventions integrating physical activity and dietary modification represent a primary strategy to mitigate cardiometabolic risk during childhood. This longitudinal intervention study investigated cardiovascular, autonomic, inflammatory, metabolic, and gut microbiome-related outcomes before and after a 4-month program combining structured physical exercise with food and nutrition education in 51 children with obesity aged 7 to 10 years. The intervention promoted favorable dietary changes, including reduced intake of saturated fatty acids (SFA), sodium, and total energy. These modifications were accompanied by a reduction in body fat percentage and systemic inflammation, evidenced by lower circulating interleukin-17A (IL-17A) and tumor necrosis factor-alpha (TNF-α) levels. Improvements in biochemical profiles were observed, including increased albumin and high-density lipoprotein cholesterol (HDL-c), and reduced serum triglyceride and urea levels. Metabolomic analyses revealed beneficial shifts in circulating phosphatidylethanolamines, phosphatidylglycerols, choline, and branched-chain amino acids (BCAA). Cardiovascular assessments demonstrated significant reductions in systolic and diastolic blood pressure and improvements in heart rate variability, indicating enhanced cardiac autonomic modulation. Gut microbiota analyses showed no differences in alpha or beta diversity; however, Bray-Curtis volatility analyses identified significant within-subject compositional shifts. Exploratory multivariate analyses suggested potential associations between specific gut taxa (e.g., Ligilactobacillus, Streptococcus, Roseburia), circulating metabolites, and cardiovascular autonomic indices, supporting the existence of microbiota-metabolite-heart interactions. In summary, a 4-month multicomponent lifestyle intervention improved cardiovascular autonomic function, inflammatory status, and cardiometabolic profiles in children with obesity. These findings highlight the cardiovascular benefits of early lifestyle modification and support integrative approaches targeting autonomic and metabolic pathways in pediatric obesity.

Objectives: Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, increasing evidence points to a pivotal role of the gut. Aiming to clarify whether metformin-induced changes in the intestinal tract directly contribute to metabolic improvement, we evaluated the effects of escalating doses (from 50 to 200 mg/kg/day) of metformin orally administered for 4 weeks in mice made glucose intolerant by ten weeks of high fat high sucrose diet. Methods: Several intestinal parameters were studied, including caecal microbiota composition and bile acids profile, ileal FXR signaling, abundance of GLP1-producing cells and goblet cells and blood metabolome. Results: Metformin restored glucose tolerance, fasting insulinemia and HOMA-IR index in a dose-dependent manner. Only a subset of gut-related effects, including mucus production and GLP-1 expression, exhibited a parallel dose–response relationship, suggesting a possible contribution to the observed metabolic improvements. In contrast, other changes, including ileal Fxr-Fgf15 inhibition and hepatic ceramide reduction did not scale with dose, suggesting they are not the main drivers of metformin dose-dependent effects on glycemic control. We also pointed out marked differential sensitivity of gut bacteria to metformin supporting complex interactions of the drug with the microbial ecosystem. Conclusion: Finally, metformin enhanced the proliferation of intestinal epithelium, resulting in increased length of ileal villi. Altogether, this study offers new insights into the metformin mechanism of action and revealed potential novel microbial biomarkers and targets for enhancing its therapeutic efficacy.

Chronic kidney disease (CKD) is characterized by accumulation of uremic toxins (UTs), such as p-cresyl sulfate and indoxyl sulfate, generated through the transformation of tyrosine and tryptophan by the gut microbiota. Using an ex vivo Simulator of the Human Intestinal Microbial Ecosystem (SHIME) colonized with fecal samples from eight CKD patients or nine healthy volunteers, a higher bacterial generation of p-cresol and indoles post-amino acid enrichment, as well lower basal butyrate levels, in the feces of CKD patients were found. Through in silico data mining, we selected a probiotic strain lacking the capacity to produce UT, i.e. without genes for tryptophanase, tyrosinase and urease. In vitro, we confirmed the potential of cellobiose as a prebiotic supporting the growth of this strain. We further designed a novel specific multi-biotic for CKD (SynCKD) [containing a probiotic Lactobacillus johnsonii NCC533, a prebiotic (1% cellobiose), and a postbiotic (1% short and medium chain triglycerides C4-C8, a source of butyrate)]. SynCKD effectively curtailed UT precursor generation ex vivo. The in vivo efficacy of SynCKD (and the synergic effect) was established in two uremic rodent models, demonstrating lower plasma levels of UTs and enhancing kidney function after 6-8 weeks of treatment. These effects were linked to better gut microbial ecology. Metagenomic analysis revealed reduced microbial genes for tryptophan/tyrosine degradation. This study lays the foundation for SynCKD as a potential therapy to mitigate CKD progression.

Bacaba (Oenocarpus bacaba Mart.) is an underexplored Amazonian fruit rich in polyphenols that can serve as a substrate for probiotic survival and may positively impact on the composition and metabolism of the intestinal microbiota. This study aimed to evaluate the bacaba pulp fermented with probiotics Lactobacillus acidophilus 05 (LA-05) and Lacticaseibacillus casei 01 (LC1) regarding the chemical composition and probiotics survivability during fermentation (48 h), and the effect on the modulation of the intestinal microbiota of healthy adults through 16S rRNA sequencing. The probiotic-fermented bacaba pulps showed decreased pH and total soluble solids values and sugar content (maltose, glucose, fructose, and rhamnose), and increased titratable acidity values, organic acid content (lactic and tartaric acids), and phenolic compounds concentration compared to the control pulp. Furthermore, it presented adequate probiotic viability after fermentation and simulated gastrointestinal conditions. The bacaba pulp fermented with LC1 showed a higher concentration of butyric acid and phenolic compounds concentration (trans-resveratrol, cis resveratrol, catechin, procyanidin B2, and pelargonidin 3-glucoside) and bioaccessibility compared to the control pulp. The bacaba pulp fermented with LA-5 showed a higher concentration of pelargonidin 3-glucoside and procyanidin B2 compared to the control pulp and the highest bioaccessibility of some phenolic compounds (trans-resveratrol, cis-resveratrol, catechin, epicatechin, procyanidin B1, procyanidin B2, myricetin, and isorhamnetin). In vitro fecal fermentation reduced the pH and increased the abundance of Desulfovibrionales, Lactobacillales, and Peptostreptococcales-Tissierellales for all treatments. Bacaba pulp with LC1 resulted in the lowest pH values, and increased production of organic acids and concentration of phenolic compounds. Furthermore, both probiotic pulps increased the abundance of Lactobacillales and Acidaminococcales and decreased the abundance of Clostridiales. These findings provide new information about the potential of using bacaba in a functional pulp that may benefit human health through colonic microbiota changes.

Osteosarcopenia, characterized by the coexistence of osteopenia/osteoporosis and sarcopenia, represents a significant health concern in geriatrics, with an increased risk of falls and fractures. The enterokine fibroblast growth factor 19 (FGF19) was recently shown to prevent muscle weakness in preclinical models. This study investigated the therapeutic potential of FGF19 in mitigating bone and muscle deterioration in aged male mice. Twenty-one-month-old C57BL/6 male mice received daily injections of human recombinant FGF19 (0.1 mg/kg) for 21 days. Histological and functional analyses revealed a shift toward larger muscle fibers in FGF19-treated mice as well as an increased muscle strength, without affecting muscle mass. In parallel, X-ray microtomography showed that FGF19 had no overt negative impact on bone, with a range of modest, site-specific, and opposing effects. In the distal femur metaphysis FGF19, it reduced cortical thickness, but significantly increased bone cross-sectional area, with an overall increased polar moment of inertia, a geometrical parameter linked to favorable mechanical properties. It also elevated cortical bone porosity in the same region. There were no significant effects on trabecular bone or cortical bone parameters in the proximal femur side at the lesser trochanter level nor at the femoral midshaft or in the tibia. In the L2 vertebra, cortical porosity decreased. Histomorphometry of trabecular bone and analysis of transcriptional output of selected genes in femurs revealed only minor changes in bone cellular activities and gene expression after three weeks of treatment. In conclusion, FGF19 treatment increased muscle strength in aged male mice, without negatively impacting aging bone.

The polarization of tissue-resident macrophages is influenced by a variety of signals from the immune system and the local tissue environment, including nutrition. Although it is known that the quality and quantity of ingested lipids have a significant effect on the lipid composition of extracellular vesicles and their fate, it is unknown how the nutritional environment modifies the release and the function of macrophage-derived EVs. In this study, we used a combination of palmitate and oleate (1:2, FFA) to generate lipid-associated TREM2-expressing macrophages (LAM/TREM2+) in vitro. Using various electron microscopy techniques (TEM, SEM, CryoEM) and fluorophores, we found that FFA overload not only induces lipid storage in LAM/TREM2+ macrophages, but also alters their morphology and reduces the diversity and the number of the lipid-derived structures they release. In addition, LAM/TREM2+ macrophages accumulated lipid droplets (LDs) below the plasma membrane and we discovered for the first time that they export and disseminate full LDs into their environment, in addition to extracellular vesicles, by using a cellular pathway associated to CD81. The use of 14C-palmitate confirmed the presence of 14C-triacylglycerols in the large extracellular vesicle pellet. LAM/TREM2+ macrophage-derived EVs induced TREM2 and Il-10 expression in recipient M0 macrophages. These data provide potential insights into how dietary factors and metabolic perturbations can shape the functions of macrophage-derived EVs in the context of metabolic diseases such as diabetes and obesity. In addition, LAM/TREM2+ macrophage-derived EVs modulated insulin-sensitivity, mitochondrial oxidative capacity, lipid profiles and the expressions of genes encoding extracellular matrix components in recipient skeletal muscle cells. Although previously postulated but never demonstrated, these data also highlight the LAM/TREM2+ macrophage-derived EVs as important players in SkM tissue renewal and metabolic homeostasis. ### Competing Interest Statement The authors have declared no competing interest.

BACKGROUND:Resistance training (RT) is the first-line treatment to improve sarcopenia features. However, increasing muscle mass with RT remains challenging and displays inconsistent results. Manipulating training variables may present a novel approach to improve muscle mass gain in sarcopenic individuals. The present study aimed to measure the effectiveness of RT alone on muscle mass outcomes in older adults with sarcopenia and determine the influence of RT variables on muscle mass improvement. METHOD:We conducted a systematic review according to PRISMA standards to gather studies that conducted a supervised RT without nutritional intervention in sarcopenia-diagnosed older adults with a muscle mass outcome versus a control group. A search strategy was performed on PubMed, Medline, Cochrane and Google Scholar in the last 14 years, from the publication of the first agreement on the diagnosis (EWGSOP, 2010). Along with sample characteristics, we extracted and analysed the following training variables: frequency (number of sessions per week), intensity (in rating perceived effort and in % of the one repetition maximal load), duration (weeks), volume (number of sets per week), periodization (yes/no) and muscle failure (yes/no). First, we standardized the outcome with Hedge's g and pooled the effect size (ES) of each study in a univariate meta-analysis adjusted for risk of bias. Then, we performed training composition comparisons between 'effective interventions' and 'ineffective interventions', which were previously classified based on the 95% confidence interval (CI) effect size. Finally, relevant variables were regressed as moderators of the weighted ES in a mixed-effects model. RESULTS:A total of 14 studies representing 528 individuals (73.1 ± 6.6 years, 385 women [73%] and 143 men [27%]) were included for analysis. A significant effect of RT to improve muscle mass was found with a small weighted ES estimate (g = 0.38 [0.18; 0.58] 95% CI, p ≤ 0.001). There was no publication bias across studies (p = 0.7). 'Ineffective interventions' included significantly older individuals (p ≤ 0.01). Training composition was homogenous between the groups. The final model showed that age was the only significant moderator of the ES (estimate = -0.06 [-0.08; -0.03] 95% CI, p ≤ 0.001). CONCLUSION:In sarcopenic older adults, designing an evidence-based RT induces significant gains in muscle mass, but training variables manipulation does not yield greater outcomes. This study also unveils that ageing with sarcopenia negatively affects the significant improvement of muscle mass induced by RT.

This study aimed to evaluate the functional, technological, and sensory aspects of mangaba (Hancornia speciosa Gomes) fruit pulp fermented with the probiotic Lacticaseibacillus casei 01 (LC1) during refrigerated storage (7 °C, 28 days). The effects of the fermented mangaba pulp on the modulation of the intestinal microbiota of healthy vegan adults were also assessed. Mangaba pulp allowed high viability of LC1 during storage and after simulated gastrointestinal conditions (≥7 log CFU/g). The fermented mangaba pulp showed lower pH and total soluble solids, and higher titratable acidity, and concentrations of lactic, acetic, citric, and propionic acids during storage compared to non-fermented pulp. Also, it presented a higher concentration of bioaccessible phenolics and volatiles, and improved sensory properties (yellow color, brightness, fresh appearance, and typical aroma and flavor). Fermented mangaba pulp added to in vitro cultured colonic microbiota of vegan adults decreased the pH values and concentrations of maltose, glucose, and citric acid while increasing rhamnose and phenolic contents. Fermented mangaba pulp promoted increases in the abundance of Dorea, Romboutsia, Faecalibacterium, Lachnospira, and Lachnospiraceae ND3007 genera and positively impacted the microbial diversity. Findings indicate that mangaba pulp fermented with LC1 has improved chemical composition and functionality, inducing changes in the colonic microbiota of vegan adults associated with potential benefits for human health.

The purpose of this study was to investigate the potential prebiotic properties of cassava cultivars from Northeast [Doce mel and Ourinho (OUR)] and South [Baiana, and IPR-Upira (UPI)] of Brazil in in vitro fermentation systems. The cultivars were evaluated for their chemical composition, and, then, two cultivars were selected (OUR and UPI) and subjected to in vitro gastrointestinal digestion to assess the effects on probiotics Lacticaseibacillus casei, Lactobacillus acidophilus, and Bifidobacterium animalis growth, metabolic activity, and prebiotic activity scores. Finally, the impact of cassava cultivars on the fecal microbiota of celiac individuals was evaluated using the 16S rRNA gene. Cassava cultivars have variable amounts of fiber, resistant starch, fructooligosaccharides (FOS), organic acids, phenolic compounds, and sugars, with OUR and UPI cultivars standing out. OUR and UPI cultivars contributed to the increase in the proliferation rates of L. casei (0.04-0.19), L. acidophilus (0.34-0.27), and B. animalis (0.10-0.03), resulting in more significant effects than FOS, an established prebiotic compound. Also, the positive scores of prebiotic activities with probiotic strains indicate OUR and UPI's ability to stimulate beneficial bacteria while limiting enteric competitors selectively. In addition, OUR and UPI promoted increased relative abundance of Bifidobacteriaceae, Enterococcaceae, and Lactobacillaceae in the fecal microbiota of celiac individuals while decreased Lachnospirales, Bacteroidales, and Oscillospirales. The results show that cassava cultivars caused beneficial changes in the composition and metabolic activity of the human intestinal microbiota of celiacs. OUR and UPI cultivars from the Northeast and South of Brazil could be considered potential prebiotic ingredients for use in the formulation of functional foods and dietary supplements.

Abstract Background and Aims Despite the demonstrated efficacy of a low-protein diet (LPD) in slowing the progression of chronic kidney disease (CKD), the underlying mechanisms remain inadequately understood. Given the potential drawbacks, including poor compliance and a risk of malnutrition, gaining insights into the molecular mechanisms driving these benefits is crucial for safe clinical translation. In this study, our objectives were to 1) assess the impact of an LPD on the metabolic health of individuals and mice with CKD; 2) investigate the hypothesis that these effects are mediated by a reduction in uremic toxins; and 3) explore whether the combination of an LPD and supplementation with a strain of Lactiplantibacillus plantarum (strain LpWJL), selected for its ability to enhance growth in a Drosophila model of diet-induced stunting, could synergistically amplify the positive effects of the LPD while minimizing its potential adverse consequences. Method We recruited CKD patients with no diabetes or prediabetes, who were randomized to a LPD and cetoanalogues (0.4 g/kg/day) (n = 5) or a normal diet (ND) (0.8 g/kg/day, n = 6) for 3 months. A glucose tolerance test was measured at baseline and after 3 months. Four groups of mice were studied: a sham group with a ND (n = 4), 5/6th nephrectomized mice with a ND (n = 7), and 5/6th nephrectomized mice with LPD (5% w/w) and LPwjl (n = 7) or placebo (n = 7) for 6 weeks. Blood samples and liver tissues were analyzed with the MxP 500 Quant® (Biocrates) kit by LC-MS/MS (XEVO TQ-XS, Waters). Results Under LPD, beta cell function showed improvement (Matsuda index, P = 0.049, and AUC insulin, P = 0.02). Although the diet did not influence body composition, the LPD group exhibited a reduction in muscle strength (P = 0.02). LPD decreased blood concentration several uremic toxins such as indoxyl sulfate and TMAO. Insulin sensitivity and beta-cell function demonstrated negative correlations with urea, TMAO, and indoxyl sulfate. Mouse studies confirmed the positive impact of LPD on glucose homeostasis but also revealed detrimental effects on lean mass and fat mass. Supplementation with LpWJL during LPD mitigated the loss of fat mass, improved the insulin tolerance test, and enhanced the reduction of certain blood uremic toxins, including indoxyl sulfate. LpWJL supplementation exerted a substantial impact on the hepatic metabolome, resulting in increased triglyceride accumulation and decreased levels of diglycerides, acylcarnitines, and phosphocholines. Conclusion We have highlighted the substantial benefits of a 3-month LPD on markers of glucose homeostasis and uremic toxins in mice and humans without diabetes. LpWJL induced profound modifications in both blood and liver metabolome and was associated with a limitation of trophic alterations in LPD diet-induced CKD mice, while also enhancing glucose homeostasis. Further studies are essential to gain a better understanding of the underlying mechanisms involved.

Background and objectiveOverweight and obesity affects millions of individuals worldwide and consequently represents a major public health concern. Individuals living with overweight and obesity have difficulty maintaining a low body weight due to known physiological mechanisms which prevent further weight loss and drive weight regain. In contrast, mechanisms which promote low body weight maintenance receive less attention and are largely unknown. To uncover these intrinsic mechanisms, we investigated a human cohort of constitutionally thin (CT) individuals which maintain a low body weight and are resistant to weight gain despite exposure to an obesogenic environment.MethodsTo identify novel genes that contribute to low body weight maintenance, we performed transcriptomics on adipose tissue biopsies collected from CT and normal body weight (NBW) individuals and identified sulfotransferase 1A1 (SULT1A1) as a target for further investigation in mice. Sult1a1 knockout (KO) mice were fed a standard diet to assess the impact of Sult1a1 deletion on metabolic traits. To determine if high-fat feeding recapitulated the CT weight gain resistance phenotype, Sult1a1 KO mice were fed a high-fat diet for 13-weeks. A subset of wild-type and Sult1a1 KO mice from the standard diet were further analyzed for characterization of adipose tissue respiratory capacity.ResultsIn comparison to NBW controls, adipose tissue from CT individuals expresses less SULT1A1. Sult1a1 KO mice weigh 10% less at the end of the study period and on a high-fat diet, Sult1a1 KO mice tended to gain less weight and had reduced fat mass at 14-weeks of age. These changes were associated with reduced fasting insulin and lessened adipose tissue inflammation and fibrosis. Subcutaneous adipose tissue from Sult1a1 KO mice on a standard chow diet had elevated leak respiration, uncoupling protein 1 (UCP1) expression and increased expression of a mitochondrial marker, VDAC, associating Sult1a1 deletion to adipose tissue browning.ConclusionsOur results associate Sult1a1 deletion with a tendency for lower body weight through remodeling of white adipose tissue towards a brown phenotype. The presence of UCP1, the expression of an additional mitochondrial protein and increased respiratory capacity suggest browning of the subcutaneous adipose tissue depot of Sult1a1 KO mice.

Nutraceuticals have been described as phytocomplexes when derived from foods of plant origin or a pool of secondary metabolites when derived from foods of animal origin, which are concentrated and administered in an appropriate form and can promote beneficial health effects in the prevention/treatment of diseases. Considering that pharmaceutical medications can cause side effects, there is a growing interest in using nutraceuticals as an adjuvant therapeutic tool for several disorders involving autonomic dysfunction, such as obesity, atherosclerosis and other cardiometabolic diseases. This review summarizes and discusses the evidence from the literature on the effects of various nutraceuticals on autonomic control, addressing the gut microbiota modulation, production of secondary metabolites from bioactive compounds, and improvement of physical and chemical properties of cell membranes. Additionally, the safety of nutraceuticals and prospects are discussed. Probiotics, resveratrol, quercetin, curcumin, nitrate, inositol, L-carnosine, and n-3 polyunsaturated fatty acids (n-3 PUFAs) are among the nutraceuticals most studied to improve autonomic dysfunction in experimental animal models and clinical trials. Further human studies are needed to elucidate the effects of nutraceuticals formulated of multitarget compounds and their underlying mechanisms of action, which could benefit conditions involving autonomic dysfunction.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain Lp WJL ) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that Lp WJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor–1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from Lp WJL , as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for Lp WJL -mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.