Allium-Derived Compound Propyl Propane Thiosulfonate (PTSO) Attenuates Metabolic Alterations in Mice Fed a High-Fat Diet through Its Anti-Inflammatory and Prebiotic Properties

Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesity-associated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ẞ, Il-6, Tnf-α, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-α, Ppar-γ, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome.     

The Anti-Obesity Effects of Lemon Fermented Products in 3T3-L1 Preadipocytes and in a Rat Model with High-Calorie Diet-Induced Obesity

Lemon (Citrus limon) has antioxidant, immunoregulatory, and blood lipid-lowering properties. This study aimed to determine the effect of the lemon fermented product (LFP) which is lemon fermented with Lactobacillus OPC1 to prevent obesity. The inhibition of lipid accumulation in 3T3-L1 adipocytes is examined using a Wistar rat model fed a high-fat diet to verify the anti-obesity efficacy and mechanism of LFP. Here, it was observed that LFP reduced cell proliferation and inhibited the lipid accumulation (8.3%) of 3T3-L1 adipocytes. Additionally, LFP reduced body weight (9.7%) and fat tissue weight (25.7%) of rats; reduced serum TG (17.0%), FFA (17.9%), glucose (29.3%) and ketone body (6.8%); and increased serum HDL-C (17.6%) and lipase activity (17.8%). LFP regulated the mRNA expression of genes related to lipid metabolism (PPARγ, C/EBPα, SREBP-1c, HSL, ATGL, FAS, and AMPK). Therefore, LFP reduces body weight and lipid accumulation by regulating the mRNA expression of genes related to lipid metabolism. Overall, our results implicate LFP as a potential dietary supplement for the prevention of obesity.     

Black Tea Reduces Diet-Induced Obesity in Mice via Modulation of Gut Microbiota and Gene Expression in Host Tissues

Black tea was reported to alter the microbiome populations and metabolites in diet-induced obese mice and displays properties that prevent obesity, but the underlying mechanism of the preventative effect of black tea on high-fat diet (HFD) induced obesity has not been elucidated. Epigenetic studies are a useful tool for determining the relationship between obesity and environment. Here, we show that the water extract of black tea (Lapsang souchong, LS) reverses HFD-induced gut dysbiosis, alters the tissue gene expression, changes the level of a major epigenetic modification (DNA methylation), and prevents obesity in HFD feeding mice. The anti-obesity properties of black tea are due to alkaloids, which are the principal active components. Our data indicate that the anti-obesity benefits of black tea are transmitted via fecal transplantation, and the change of tissue gene expression and the preventative effects on HFD-induced obesity in mice of black tea are dependent on the gut microbiota. We further show that black tea could regulate the DNA methylation of imprinted genes in the spermatozoa of high-fat diet mice. Our results show a mechanistic link between black tea, changes in the gut microbiota, epigenetic processes, and tissue gene expression in the modulation of diet-induced metabolic dysfunction.     

Beneficial Effects of Partly Milled Highland Barley on the Prevention of High-Fat Diet-Induced Glycometabolic Disorder and the Modulation of Gut Microbiota in Mice

The nutritional functions of highland barley (HB) are superior to those of regular cereals and have attracted increasing attention in recent years. The objective of this study was to investigate whether partly milled highland barley (PHB) can regulate the serum glucose and lipid disorders of mice fed a high-fat diet (HFD) and to further explore their potential gut microbiota modulatory effect. Our results showed that PHB supplementation significantly reduced fasting blood glucose (FBG) and improved oral glucose tolerance. Histological observations confirmed the ability of PHB to alleviate liver and intestine damage. Furthermore, the results of 16S amplicon sequencing revealed that PHB prevented a HFD-induced gut microbiota dysbiosis, enriching some beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Ileibacterium, and reducing several HFD-dependent taxa (norank_f_Desulfovibrionaceae, Blautia, norank_f_Lachnospiraceae, unclassified_f_Lachnospiraceae, and Colidextribacter). In addition, the increase of Lactobacillus and Bifidobacterium presence has a slightly dose-dependent relationship with the amount of the added PHB. Spearman correlation analysis revealed that Lactobacillus and Bifidobacterium were negatively correlated with the blood glucose level of the oral glucose tolerance test. Overall, our results provide important information about the processing of highland barley to retain its hypoglycemic effect and improve its acceptability and biosafety.     

Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom.     

The Ameliorative Effect and Mechanisms of Ruditapes philippinarum Bioactive Peptides on Obesity and Hyperlipidemia Induced by a High-Fat Diet in Mice

In this study, bioactive peptides (RBPs) from Ruditapes philippinarum were prepared by fermentation with Bacillus natto and the effect and mechanisms of RBPs on obesity and hyperlipidemia were explored in mice. We found that RBPs significantly reduced body weight, adipose tissue weight, accumulation of hepatic lipids, and serum levels of total cholesterol (CHO), triglyceride (TG), and low-density lipoprotein (LDL). Mechanistic studies showed that RBPs up-regulated the hepatic expression of genes related to lipolysis, such as hormone-sensitive lipase (HSL), phosphorylated AMP-activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptors α (PPARα), and down-regulated the expression of peroxisome proliferator-activated receptors γ (PPARγ) which is related to lipid synthesis. In addition, RBPs could attenuate obesity and hyperlipidemia by regulating disordered gut microbiota composition, such as increasing the abundance of microflora related to the synthesis of short chain fatty acids (SCFAs) (Bacteroidetes, Prevotellaceas_UCG_001, norank_f_Muribaculaceae, and Odoribacter) and controlling those related to intestinal inflammation (reduced abundance of Deferribacteres and increased abundance of Alistipes and ASF356) to exert anti-obesity and lipid-lowering activities. Our findings laid the foundation for the development and utilization of RBPs as a functional food to ameliorate obesity and hyperlipidemia.     

Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress

Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic mild stress (UCMS) was used to assess the effects of IAA administration (50 mg/kg). Treatment with IAA for 5 weeks attenuated depression and anxiety-like behaviours, improved hypothalamus–pituitary–adrenal axis dysfunction and increased brain-derived neurotrophic factor expression. IAA supplementation also enhanced the serotonin pathway in the brain and gut. UCMS caused an imbalance of microbial indole metabolites in the colon, whereas IAA treatment reversed this. However, IAA intake did not affect the concentrations of indoles in the brain. Intestinal bacteria in different sections of the gut were altered by IAA treatment, with the colon showing more changes than other segments. The gut microbiome in the colon had increased proportions of Ruminococcaceae UCG013, Ruminiclostridium 6, Prevotella, Alloprevotella and Bacteroides species, which can produce short-chain fatty acids and indole derivatives. Cumulatively, our study highlights the potential of IAA treatment to alleviate mood disorders and offers a theoretical basis for understanding the antidepressant effects of IAA.     

The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.     

Effects of Probiotics and Synbiotics on Weight Loss in Subjects with Overweight or Obesity: A Systematic Review

Intestinal microbiota has been shown to be a potential determining factor in the development of obesity. The objective of this systematic review is to collect and learn, based on the latest available evidence, the effect of the use of probiotics and synbiotics in randomized clinical trials on weight loss in people with overweight and obesity. A search for articles was carried out in PubMed, Web of science and Scopus until September 2021, using search strategies that included the terms “obesity”, “overweight”, “probiotic”, “synbiotic”, “Lactobacillus”, “Bifidobacterium” and “weight loss”. Of the 185 articles found, only 27 complied with the selection criteria and were analyzed in the review, of which 23 observed positive effects on weight loss. The intake of probiotics or synbiotics could lead to significant weight reductions, either maintaining habitual lifestyle habits or in combination with energy restriction and/or increased physical activity for an average of 12 weeks. Specific strains belonging to the genus Lactobacillus and Bifidobacterium were the most used and those that showed the best results in reducing body weight. Both probiotics and synbiotics have the potential to help in weight loss in overweight and obese populations.     

Blueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics

The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.     

Long-Term Effects of Bariatric Surgery on Gut Microbiota Composition and Faecal Metabolome Related to Obesity Remission

Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.     

Synbiotic Intervention with an Adlay-Based Prebiotic and Probiotics Improved Diet-Induced Metabolic Disturbance in Mice by Modulation of the Gut Microbiota

Metabolic syndrome and its associated conditions, such as obesity and type 2 diabetes mellitus (T2DM), are a major public health issue in modern societies. Dietary interventions, including microbiota-directed foods which effectively modulate the gut microbiome, may influence the regulation of obesity and associated comorbidities. Although research on probiotics and prebiotics has been conducted extensively in recent years, diets with the use of synbiotics remain relatively unexplored. Here, we investigated the effects of a novel synbiotic intervention, consisting of an adlay seed extrusion cooked (ASEC)-based prebiotic and probiotic (Lactobacillus paracasei and Bacillus coagulans) on metabolic disorders and microbial dysbiosis in high-fat diet (HFD)-induced obese mice. The ASEC-based synbiotic intervention helped improve HFD-induced body weight gain, hyperlipidemia, impaired glucose tolerance, insulin resistance, and inflammation of the adipose and liver tissues. In addition, data from fecal metagenomics indicated that the ASEC-based synbiotic intervention fostered reconstitution of gut bacterial diversity and composition in HFD-induced obese mice. In particular, the ASEC-based synbiotic intervention increased the relative abundance of families Ruminococcaceae and Muribaculaceae and order Bacteroidales and reduced that of families Lactobacillaceae, Erysipelotrichaceae, and Streptococcaceae in HFD-induced obese mice. Collectively, our results suggest that delayed dietary intervention with the novel ASEC-based synbiotic ameliorates HFD-induced obesity, metabolic disorders, and dysbiosis.     

Impact of Exercise on Gut Microbiota in Obesity

Physical activity, exercise, or physical fitness are being studied as helpful nonpharmacological therapies to reduce signaling pathways related to inflammation. Studies describing changes in intestinal microbiota have stated that physical activity could increase the microbial variance and enhance the ratio of Firmicutes/Bacteroidetes, and both actions could neutralize the obesity progression and diminish body weight. The aim of this review is to provide an overview of the literature describing the relationship between physical activity profiles and gut microbiota and in obesity and some associated comorbidities. Promoting physical activity could support as a treatment to maintain the gut microbiota composition or to restore the balance toward an improvement of dysbiosis in obesity; however, these mechanisms need to be studied in more detail. The opportunity to control the microbiota by physical activity to improve health results and decrease obesity and related comorbidities is very attractive. Nevertheless, several incompletely answered questions need to be addressed before this strategy can be implemented.     

The Impact of Obesity and a High-Fat Diet on Clinical and Immunological Features in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiple organ involvement predominantly affecting women of childbearing age. Environmental factors, as well as genetic predisposition, can cause immunological disturbances that manifest as SLE. A habitual high-fat diet and obesity have recently been reported to play a role in the pathogenesis of autoimmune diseases. The frequency of obesity is higher in patients with SLE than in general populations. Vitamin D and adipokines, such as leptin and adiponectin, are possible mediators connecting obesity and SLE. Serum leptin and adiponectin levels are elevated in patients with SLE and can impact innate and adaptive immunity. Vitamin D deficiency is commonly observed in SLE. Because vitamin D can modulate the functionality of various immune cells, we review vitamin D supplementation and its effects on the course of clinical disease in this work. We also discuss high-fat diets coinciding with alterations of the gut microbiome, or dysbiosis. Contingent upon dietary habits, microbiota can be conducive to the maintenance of immune homeostasis. A high-fat diet can give rise to dysbiosis, and patients who are affected by obesity and/or have SLE possess less diverse microbiota. Interestingly, a hypothesis about dysbiosis and the development of SLE has been suggested and reviewed here.     

Adzuki Bean Alleviates Obesity and Insulin Resistance Induced by a High-Fat Diet and Modulates Gut Microbiota in Mice

Adzuki bean consumption has many health benefits, but its effects on obesity and regulating gut microbiota imbalances induced by a high-fat diet (HFD) have not been thoroughly studied. Mice were fed a low-fat diet, a HFD, and a HFD supplemented with 15% adzuki bean (HFD-AB) for 12 weeks. Adzuki bean supplementation significantly reduced obesity, lipid accumulation, and serum lipid and lipopolysaccharide (LPS) levels induced by HFD. It also mitigated liver function damage and hepatic steatosis. In particular, adzuki bean supplementation improved glucose homeostasis by increasing insulin sensitivity. In addition, it significantly reversed HFD-induced gut microbiota imbalances. Adzuki bean significantly reduced the ratio of Firmicutes/Bacteroidetes (F/B); enriched the occurrence of Bifidobacterium, Prevotellaceae, Ruminococcus_1, norank_f_Muribaculaceae, Alloprevotella, Muribaculum, Turicibacter, Lachnospiraceae_NK4A136_group, and Lachnoclostridium; and returned HFD-dependent taxa (Desulfovibrionaceae, Bilophila, Ruminiclostridium_9, Blautia, and Ruminiclostridium) back to normal status. PICRUSt2 analysis showed that the changes in gut microbiota induced by adzuki bean supplementation may be associated with the metabolism of carbohydrates, lipids, sulfur, and cysteine and methionine; and LPS biosynthesis; and valine, leucine, and isoleucine degradation.     

The Role of Short-Chain Fatty Acids in Mediating Very Low-Calorie Ketogenic Diet-Infant Gut Microbiota Relationships and Its Therapeutic Potential in Obesity

As the very low-calorie ketogenic diet (VLCKD) gains increased interest as a therapeutic approach for many diseases, little is known about its therapeutic use in childhood obesity. Indeed, the role of VLCKD during pregnancy and lactation in influencing short chain fatty acid (SCFA)-producing bacteria and the potential mechanisms involved in the protective effects on obesity are still unclear. Infants are characterized by a diverse gut microbiota composition with higher abundance of SCFA-producing bacteria. Maternal VLCKD during pregnancy and lactation stimulates the growth of diverse species of SCFA-producing bacteria, which may induce epigenetic changes in infant obese gene expression and modulate adipose tissue inflammation in obesity. Therefore, this review aims to determine the mechanistic role of SCFAs in mediating VLCKD-infant gut microbiota relationships and its protective effects on obesity.     

Effects of Fermented Milk Containing Bifidobacterium animalis Subsp. lactis MN-Gup (MN-Gup) and MN-Gup-Based Synbiotics on Obesity Induced by High Fat Diet in Rats

Given the probiotic effects previously found in Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) and its great application potential in dairy products, this study aimed to investigate the effects of fermented milk containing MN-Gup or MN-Gup-based synbiotics on high fat diet (HFD)-induced obesity in rats. Galacto-oligosaccharides (GOS) and xylo-oligosaccharides (XOS) were selected as the tested prebiotics in MN-Gup-based synbiotics due to their promotion of MN-Gup growth in vitro. After nine weeks of HFD feeding, the obese rats were intervened with fermented milk containing MN-Gup (MN-Gup FM) or its synbiotics (MN-Gup + GOS FM, MN-Gup + XOS FM) for eight weeks. The results showed that the interventions could alleviate HFD-induced body weight gain, epididymal fat deposition, adipocyte hypertrophy, dyslipidemia and inflammation, but GOS and XOS did not exhibit significant synergies with MN-Gup on those alleviations. Furthermore, the interventions could regulate the HFD-affected gut microbiota and microbial metabolites, as shown by the increases in short chain fatty acids (SCFAs) and alterations in obesity-related bile acids (BAs), which may play important roles in the mechanism underlying the alleviation of obesity. This study revealed the probiotic effects of MN-Gup on alleviating obesity and provided the basis for MN-Gup applications in the future.     

Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice via Modulating Inflammation and Intestinal Microbiota

Inflammatory activation and intestinal flora imbalance play an essential role in the development and progression of colorectal cancer (CRC). Berberine (BBR) has attracted great attention in recent years due to its heath-related benefits in inflammatory disorders and tumors, but the intricate mechanisms have not been fully elucidated. In this study, the effects and the mechanism of BBR on colon cancer were investigated in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated carcinogenesis mice model. Our results showed that pre-administration of BBR showed a decrease in weight loss, disease activity index (DAI) score, and the number of colon tumors in mice, compared with the model group. The evidence from pathological examination indicated that the malignancy of intestinal tumors was ameliorated after pre-administration of BBR. Additionally, pre-administration with BBR suppressed the expression of pro-inflammatory factors (interleukin (IL)-6, IL-1β, cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α) and the cell-proliferation marker Ki67, while expression of the tight junction proteins (ZO-1 and occludin) were increased in colon tissue. Moreover, the levels of critical pathway proteins involved in the inflammatory process (p-STAT3 and p-JNK) and cell cycle regulation molecules (β-catenin, c-Myc and CylinD1) exhibited lower expression levels. Besides, 16S rRNA sequence analysis indicated that pre-administration of BBR increased the ratio of Firmicutes/Bacteroidetes (F:M) and the relative abundance of potentially beneficial bacteria, while the abundance of cancer-related bacteria was decreased. Gavage with Lactobacillus rhamnosus can improve the anti-tumor effect of BBR. Overall, pre-administration of BBR exerts preventive effects in colon carcinogenesis, and the mechanisms underlying these effects are correlated with the inhibition of inflammation and tumor proliferation and the maintenance of intestinal homeostasis.