Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding Porphyromonadaceae, Campylobacteraceae, Prevotellaceae, Actimomycetaceae, Veillonellaceae, Anaerivoracaceae, Fusobacteriaceae, and the Clostridium family XI 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while Pseudomonadaceae and Micrococcacecae, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5-10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.

Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

Microplastics (MPs) are pervasive in the environment and food. The potential health hazards of this emerging pollutant have raised significant concerns in recent years. However, the underlying mechanism by which MPs have any impact on brown and beige adipocytes in the context of obesity is yet to be investigated.

The C57BL/6 J mice were randomly assigned to the HFD and HFD+MPs group for 12 weeks of exposure to explore the differences in brown and beige adipocyte function. The gut microbiota analysis, fecal microbiota transplantation and metabolomic profiling were carried out to further determine its potential mechanism.

The present work demonstrated that high-fat diet mice accumulate lipids and have reduced energy expenditure after three months of oral administration of MPs. In addition to escalating intestinal dysbiosis, exposing HFD mice to MPs induces thermogenic dysfunction in inguinal white adipose tissue and brown adipose tissue. Following the fecal microbiota transplantation, the accumulation of lipids and dysfunction in energy expenditure within the microbiota of recipient mice further elucidated the inhibitory effect of MPs.

Our results suggest that MPs induced the thermogenic dysfunction of BAT and iWAT by affecting gut microbiota composition. The present study highlights the mechanisms by which MPs produce thermogenic dysfunction in BAT and iWAT and disruption in the gastrointestinal microbiota.

Obesity and its associated pro-inflammatory activity contribute significantly to metabolic dysfunction. In contrast, browning of white adipose tissue (WAT) generally improves metabolic health. Our prior research suggested that macrophage-derived pro-inflammatory cytokines suppress key regulators of browning-adrenergic receptor β3 (Adrb3) and peroxisome proliferator-activated receptor γ (Pparg)-as well as energy metabolism mediators-insulin receptor substrate 1 (Irs1) and hormone-sensitive lipase (Lipe)-in diet-induced obese mice. To explore this mechanism, we developed an in vitro model using RAW264.7 macrophages and 3T3-L1 adipocytes exposed to palmitic acid (PA) and/or lipopolysaccharide (LPS). PA (200 μM) and LPS (1.0 μg/ml) synergistically promoted M1 polarization of macrophages and secretion of pro-inflammatory cytokines, with tumor necrosis factor-α (TNFα), C-C motif chemokine ligand 2 (CCL2), CCL5, and interleukin-6 (IL-6) being predominant. Conditioned media from both control and PA-treated macrophages, when exposed to LPS ≥0.01 μg/ml, significantly downregulated Adrb3, Pparg, Irs1, and Lipe in adipocytes. At physiologically relevant LPS levels (≤0.001 μg/ml), PA-treated macrophage media exerted greater suppression of these genes than controls. Among the cytokines, TNFα emerged as the primary mediator, significantly reducing expression of the four key regulators. Furthermore, adipocytes treated with TNFα exhibited significant reductions in both uncoupling protein 1 (Ucp1) expression and mitochondrial respiration. These findings demonstrate that exposure to obesity-associated factors (PA and LPS) induces macrophage-derived TNFα, which suppresses browning and mitochondrial function in adipocytes. This mechanism may inform new therapeutic strategies targeting TNFα to alleviate obesity-related metabolic disorders.

Fluoride can prevent dental caries by inhibiting demineralization and promoting remineralization of teeth while affecting the physiology of oral microbiota, thus inhibiting cellular enzymes. However, the effect of systemic fluoride on gut microbiota is unknown.

To explore the impacts of systemic fluoride on gut microbiota composition and abundance and associated functions such as gene and metabolic regulation.

A systematic database search was conducted of MEDLINE, Web of Science, Scopus, PubMed, CINAHL, and Embase to find articles on studies reporting the effects of fluoride on gut microbiota.

Forty-nine studies were included (n = 42 in animals, 4 of humans, 3 in vitro studies) after screening for title, abstract, and full text using Covidence to check against eligibility criteria. Data were extracted using Covidence and study quality was assessed using the Mixed Method Appraisal Tool by 2 reviewers independently.

Two human studies of dental fluorosis and 1 of patients with breast cancer (intestinal fluorine-18 fluorodeoxyglucose uptake) showed significant differences in gut microbial composition, with increased relative abundance of Acidobacteria and Proteobacteria, and decreased abundance of Firmicutes and Bacteroidetes. An ex vivo study of human feces indicated that ≤ 2 mg L-1 NaF might boost "health-associated" taxa, but concentrations (≥ 10 mg L-1 NaF) could increase the ratio of some unhealthy microbes after 24 hours. The animal studies examined the effects of high fluoride doses in water and diet (50-1200 mg L-1 NaF) for long-term (1-6 months) and short-term (6 hours to 7 days) exposure, with all showing a significant disturbance in the Firmicutes to Bacteroidota ratio.

In humans, high doses potentially may be detrimental to the microbiome, whereas ≤ 2 mg L-1 NaF had positive effects. Similarly, in animals, ≥ 50 mg L-1 NaF was unsafe, whereas ≤ 25 mg L-1 NaF had harmless effects.

PROSPERO registration No. CRD42022347357.

Prebiotics, particularly non-digestible carbohydrates (NDCs), are increasingly recognized for their role in modulating immune responses in the gut, lungs, and urinary tract. This review systematically evaluates evidence from human studies on the effects of NDCs and prebiotics on immune markers, infection risk and severity, inflammation, and vaccine responses. Prebiotics such as inulin, galactooligosaccharides (GOS), and fructooligosaccharides (FOS) positively influence gut microbiota by promoting beneficial species like Bifidobacteria. They also enhance the production of short-chain fatty acids (SCFAs) like butyrate, which interact with immune cells via G-protein-coupled receptors, inducing anti-inflammatory effects. In addition to microbiota-mediated mechanisms, NDCs and prebiotics may directly affect immune and epithelial cells by interacting with pattern recognition receptors (PRRs), enhancing gut barrier function, and modulating immunity. A systematic review of human studies showed that prebiotics, including GOS, FOS, and 2'-fucosyllactose (2FL), reduced infections and increased IgA in healthy infants, while yeast β-glucan reduced respiratory infection symptoms in healthy adults. Yeast β-glucan and GOS supplementation resulted in improvements in NK cell activity. Some effects on vaccine efficacy were noted in young adults, but the overall impact of NDCs and prebiotics on vaccination and systemic inflammation was inconsistent. Further research is needed to clarify the mechanisms involved and to optimize health applications.

Prediabetes represents a pivotal stage in the development and pathogenesis of diabetes, during which notable alterations in the gut microbiota can be observed. Vitamin D (VD) showed anti-diabetic properties, but it is unknown whether the improvement of VD on hyperglycemia is associated with gut microbiota. Thus, our objective was to investigate and verify the effects of VD3 on glucose metabolism in prediabetes, as well as to elucidate the underlying mechanisms. In this study, different concentrations of VD3 were intraperitoneally administered to prediabetic mice induced by high fat diet for 16 weeks. Biochemical analyses, oral glucose tolerance test, 16S rRNA and untargeted metabolomics were used, the mechanism was explored. Then, fecal suspensions collected from the above donors were transplanted into KKay mice for 6 weeks, and the relevant indicators were measured. The results showed that VD3 intervention alleviated glucose metabolism in KKay mice. It increased the protein expression of colon tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced tumor necrosis factor alpha (TNFα) induced toll-like receptor 4/nuclear factor kappa-B (TLR4/NFκB) and improvement of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) insulin signaling pathway. VD3 affected the structure of gut microbiota and metabolites, and functional prediction analysis suggested that VD3 may affect carbohydrate. Besides, the effect of VD3 could be delivered by fecal microbiota transplantation (FMT). Consequently, VD3 ameliorate glucose metabolism by modulating gut microbiota and metabolites in KKay mice, and this ability could be transferred by FMT.

Obesity is associated with impaired hippocampal-dependent memory, but the mechanisms driving this pathology are not fully understood. Western diets (WD) contribute to obesity, and previous reviews have described a role for WD in impaired hippocampal-dependent memory. However, there is need for a more detailed description of the pathways by which WD may impair memory. The short vs long-term effect of specific dietary components on brain structure and functions as well as the precise mechanism and molecular pathways involved are still not fully understood. This review focuses on the mechanisms and effects of gut microbiota-driven neuroinflammation. WD leads to changes and imbalance in bacterial taxa abundances that are deleterious to the host health (gut dysbiosis) and studies in rodent models show these changes are sufficient to impair hippocampal-dependent memory. Here, we discuss a variety of proposed mechanisms linking microbiota composition to hippocampal function, with a focus on neuroinflammation. Gut microbiota impacts gastrointestinal barrier function, leading to increased circulating proinflammatory bacterial products, increased blood-brain barrier permeability, and neuroinflammation.

The gut dysbiosis has been observed in gestational diabetes mellitus (GDM). However, changes in bacterial population are different among various countries due to genetic, environmental, and dietary differences. We compared the gut dominant phylum and some genus in GDM versus normo-glycemic pregnant in Iranian population, considering dietary intake. In this case-control study, 50 women diagnosed with GDM and 50 healthy pregnant, aged 18-35 yrs, during spring and summer, were participated. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Groups criteria. The bacterial populations were determined based on 16SrRNA gene expression. Actinomycetota (p = 0.02), and Bifidobacterium spp. (p = 0.001) was significantly higher in the gut of healthy mothers than the GDM. However, bacteroides was significantly higher in the gut of GDM mothers than the healthies (p = 0.02). Daily calorie intake showed a negative correlation with population of Bacteroidota (p = 0.04) and Actinomycetota (p = 0.009), but dietary carbohydrate and fat showed a positive correlation. Increase in dietary intake of mono- and poly-unsaturated fatty acids (MUFAs and PUFAs) was associated with higher Bacteroidota in the gut (p = 0.02 and p = 0.04). However, dietary cholesterol showed a negative correlation with population of Bacteroidota and Bifidobacterium spp. (p = 0.003 and p = 0.02). GDM was correlated with the gut dysbiosis. Daily calorie and cholesterol intake was positively associated with dysbiosis. However total intake of carbohydrates, MUFAs and PUFAs showed a protective effect.

The gut microbiome refers to the collective genomes of the approximately 1,000-1,150 microbial species found in the human gut, called the gut microbiota. Changing the gut microbiota composition has been shown to affect cardiovascular health significantly. Numerous studies have demonstrated the part that gut microbiota and its metabolites play in the development and course of several illnesses, including colon cancer, heart failure, stroke, hypertension, and inflammatory bowel disease. With cardiovascular diseases responsible for more than 31% of all fatalities globally, conditions like hypertension, atherosclerosis, and heart failure are serious global health issues. Developing preventive measures to fight cardiovascular diseases requires understanding how the gut microbiota interacts with the cardiovascular system. Understanding the distinctive gut microbiota linked to cardiovascular diseases has been made possible by microbial sequencing analysis. The gut microbiota and cardiovascular diseases are closely related, and more profound knowledge of this association may result in treatment strategies and broad guidelines for enhancing cardiovascular health through gut microbiome modification. This review summarizes the role of gut microbiota in cardiovascular diseases, highlighting their influence on disease progression and potential therapeutic implications.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern linked to the increasing prevalence of metabolic syndrome, including obesity and type 2 diabetes (T2D). MASLD remains a significant clinical challenge due to the absence of effective therapeutic interventions. Intermittent fasting (IF) has emerged as a promising non-pharmacological strategy for managing MASLD. Although the exact mechanisms underpinning the possible beneficial effects of IF on MASLD are not yet fully elucidated, the gut microbiota and its metabolic byproducts are increasingly recognized as potential mediators of these effects. The gut-liver axis may act as an important conduit through which IF exerts its beneficial influence on hepatic function. This review comprehensively examines the impact of various IF protocols on gut microbiota composition, investigating the resultant alterations in microbial diversity and metabolomic profiles, and their potential implications for liver health and the improvement of MASLD.

Obesity, characterized by excessive fat accumulation, stems from an imbalance between energy intake and expenditure, with the gut microbiota playing a crucial role. This review highlights how gut microbiota influences metabolic pathways, inflammation, and adipose tissue regulation in obesity. Specific bacteria and metabolites, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), modulate gut permeability, inflammation, and energy harvest, impacting obesity development. Certain gut bacteria, including Clostridium XIVb, Dorea spp., Enterobacter cloacae, and Collinsella aerofaciens, promote obesity by increasing energy harvest, gut permeability, and inflammatory response through LPS translocation into the bloodstream. Conversely, beneficial bacteria like Akkermansia muciniphila, Lactobacillus spp., and Bifidobacterium spp. enhance gut barrier integrity, regulate SCFA production, and modulate fasting-induced adipose factor, which collectively support metabolic health by reducing fat storage and inflammation. Metabolites such as SCFAs (acetate, propionate, and butyrate) interact with G-protein coupled receptors to regulate lipid metabolism and promote the browning of white adipose tissue (WAT), thus enhancing thermogenesis and energy expenditure. However, LPS contributes to insulin resistance and fat accumulation, highlighting the dual roles of these microbial metabolites in both supporting and disrupting metabolic function. Therapeutic interventions targeting gut microbiota, such as promoting WAT browning and activating brown adipose tissue (BAT), hold promise for obesity management. However, personalized approaches are necessary due to individual microbiome variability. Further research is essential to translate these insights into microbiota-based clinical therapies.

Obesity is a significant health concern, significantly contributing to increased morbidity and mortality by disrupting multiple physiological systems. It is strongly associated with metabolic dysfunctions, including impaired glycemic homeostasis, compromised intestinal barrier integrity, and gut microbiota imbalances, all exacerbating the risk of chronic diseases. The hydroalcoholic extract of açaí seeds (ASE), rich in phenolic compounds, has demonstrated beneficial effects on obesity and hyperglycemia; however, its impacts on gut health and gut-hypothalamus communication remain unclear. This study aimed to investigate the therapeutic effect of ASE in intestinal and hypothalamic alterations associated with obesity and compare it with Metformin. Male C57BL/6 mice were fed a high-fat or standard diet for 14 weeks. The ASE (300 mg/kg/day) and Metformin (300 mg/kg/day) treatments started in the tenth week until the fourteenth week, totaling four weeks of treatment. Our data show that the treatment with ASE and Metformin reduced body weight, ameliorated lipid profile, hyperglycemia, and plasma hyperleptinemia, and decreased the oxidative damage in the gut by reducing immunostaining of 8-isoprostane and NOX-4 expression, and improved the intestinal parameters and hypothalamic gene expression. Obesity-induced dysbiosis in the HF group was marked by reduced Proteobacteria and elevated LPS plasma levels, which were improved by treatments with ASE and Metformin. These findings suggest that ASE and Metformin are promising strategies to counteract the adverse effects of obesity on intestinal health and gut-hypothalamus communication, though they act through distinct mechanisms. Therefore, we can suggest that ASE is a promising natural product for treating the intestinal alterations associated with obesity.

Theabrownin has demonstrated metabolic-modulating effects, but the doses used in previous studies are difficult to achieve through regular tea consumption. This study reassesses its hypoglycemic effects at physiologically relevant doses in the db/db mouse model of type 2 diabetes mellitus (T2DM), with a focus on intestinal microbiota and metabolic pathways. The findings show that theabrownin delays glucose absorption by inhibiting α-glucosidase in the duodenum. It also reduces lipopolysaccharide (LPS)-producing bacteria, increases Akkermansia muciniphila abundance, lowers serum LPS levels, and alleviates β-cell dysfunction due to oxidative stress. Additionally, theabrownin promotes the microbial indole pathway of tryptophan metabolism, enhancing glucagon-like peptide-1 (GLP-1) secretion, which helps mitigate β-cell dysfunction. In conclusion, theabrownin shows potential as a dietary supplement for T2DM treatment, primarily regulating LPS/GLP-1 levels and restoring pancreatic islet function. These findings highlight the potential role of fermented tea in glucose metabolism regulation.

Western diets are linked to metabolic disorders such as Type 2 diabetes mellitus (T2DM) and diabetic dyslipidemia, which involve hyperglycemia, insulin resistance, high plasma cholesterol levels and altered lipoprotein profiles. The T2DM progression also involves glucolipotoxicity, wherein elevated glucose and fatty acid levels induce oxidative stress and inflammation. Excessive intake of saturated fats and/or cholesterol can trigger dysbiosis, which weakens the colonic barrier, increases its permeability, and promotes chronic low-grade inflammation, thereby accelerating the progression of T2DM. Silicon, an essential trace element, has demonstrated antidiabetic, hypolipidemic, antioxidant and anti-inflammatory properties, suggesting its potential as a nutritional adjuvant in therapeutic management of T2DM and the maintenance of gut health. In this study, 24 male Wistar rats were divided into three groups: (1) an early-stage T2DM group (ED) fed a control meat incorporated into a high saturated-fat diet; (2) a late-stage T2DM group (LD) fed a control meat incorporated into a high-saturated fat and high cholesterol diet combined with streptozotocin and nicotinamide injection; and (3) a late-stage T2DM group fed a silicon enriched meat (LD-Si). Microbiota composition, lipoperoxidation and concentrations of fat, cholesterol, oxysterols and short-chain fatty acids and silicon were assayed in feces. The colonic tissue morphology, barrier integrity, antioxidant capacity and inflammatory markers were measured to evaluate the impact of silicon on colonic health and intestinal barrier function. Silicon enriched meat (Si-RM) consumption increased faecal fat and cholesterol excretion and reduced toxic luminal environments by modulating oxysterols. Si-RM consumption also enhanced colonic barrier integrity, increasing tight junction proteins and goblet cells, and exhibited antioxidant effects via the pNrf2 pathway and superoxide dismutase activity. Furthermore, silicon reduced the pro-inflammatory cytokines TNFα and IL-6, likely through inhibition of the TLR4/NFκB pathway. The results suggest that silicon's ability to enhance intestinal barrier integrity, reduce oxidative stress, and prevent inflammation could slow down T2DM progression, making it a promising nutritional adjuvant for managing the disease.

The purpose of this study was to investigate the relationship between the Dietary Index for Gut Microbiota (DI-GM) and hyperlipidemia (HL). The DI-GM, a novel index for assessing gut microbiota diversity, has not yet been thoroughly examined in relation to HL.

This research involved a cohort of 13,529 individuals enrolled from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2020. We applied restricted cubic spline (RCS) analysis and weighted multivariable logistic regression to assess the association between DI-GM and HL, supplemented by subgroup analyses to reinforce these findings.

After multivariable adjustment, subjects with high intake of DI-GM were determined to have a significant reduced risk for developing HL, with a 5% reduced risk for HL for each one standard deviation increased in DI-GM (P = 0.01). In contrast with the group with a DI-GM < 3, HL in the group with a DI-GM > 6 was 40% reduced (P < 0.001). RCS analysis showed a negative linear dose-response relation between DI-GM and development of HL. Subgroup analysis showed an interaction between age-stratification and DI-GM (P = 0.01), but not with gender, racial, BMI, diabetes, and hypertension groups (P > 0.05).

Our study results show a significant negative linear correlation between DI-GM and HL. However, further research is needed to confirm our findings.

Most forms of obesity are associated with chronic diseases that remain a global public health challenge.

Despite significant advancements in understanding its pathophysiology, effective management of obesity is hindered by the persistence of knowledge gaps in epidemiology, phenotypic heterogeneity and policy implementation.

This consensus statement by the European Society for Clinical Investigation identifies eight critical areas requiring urgent attention. Key gaps include insufficient long-term data on obesity trends, the inadequacy of body mass index (BMI) as a sole diagnostic measure, and insufficient recognition of phenotypic diversity in obesity-related cardiometabolic risks. Moreover, the socio-economic drivers of obesity and its transition across phenotypes remain poorly understood.

The syndemic nature of obesity, exacerbated by globalization and environmental changes, necessitates a holistic approach integrating global frameworks and community-level interventions. This statement advocates for leveraging emerging technologies, such as artificial intelligence, to refine predictive models and address phenotypic variability. It underscores the importance of collaborative efforts among scientists, policymakers, and stakeholders to create tailored interventions and enduring policies.

The consensus highlights the need for harmonizing anthropometric and biochemical markers, fostering inclusive public health narratives and combating stigma associated with obesity. By addressing these gaps, this initiative aims to advance research, improve prevention strategies and optimize care delivery for people living with obesity.

This collaborative effort marks a decisive step towards mitigating the obesity epidemic and its profound impact on global health systems. Ultimately, obesity should be considered as being largely the consequence of a socio-economic model not compatible with optimal human health.

Bacterial extracellular vesicles (EVs) are produced by both Gram-negative and Gram-positive bacteria. These EVs are composed of lipid bilayers and various components derived from parent bacteria, including proteins, lipids, and nucleic acids. Previous studies have indicated the significant role of bacterial EVs in interactions between bacteria and between bacteria and hosts. Moreover, bacterial EVs are emerging as promising delivery vectors capable of transporting drug molecules over long distances to tissues. Therefore, understanding the biogenesis of bacterial EVs and how to regulate their production holds great importance for expanding their applications. In this review, we provide an overview of bacterial EVs, especially focusing on the distinct mechanisms of EVs biogenesis and the regulation of EVs production in both Gram-negative and Gram-positive bacteria. Additionally, we discuss various methods for cargos loading into bacteria EVs, as well as their diverse applications in vaccines, cancer therapy, and drug delivery. We anticipate that this review will advance the field of bacterial EVs, contributing to both the enhancement of existing applications and the emergence of novel applications.

Obesity is associated with skeletal deterioration and increased fracture risk, but the underlying mechanism is unclear. Herein, it is shown that obese gut microbiota promotes skeletal deterioration by inducing bone marrow macrophages (BMMs) senescence and grancalcin (GCA) secretion. Obese mice and those receiving obese fecal microbiota transplants exhibit increased senescent macrophages and elevated GCA expression in the bone marrow. In a study of 40 participants, it is found that obese patients are associated with higher serum GCA levels. It is further revealed that obese gut-microbiota derived lipopolysaccharides (LPS) stimulate GCA expression in senescent BMMs via activating Toll-like receptor 4 pathway. Mice with depletion of the Gca gene are resistant to the negative effects of obesity and LPS on bone. Moreover, neutralizing antibody against GCA mitigates skeletal deterioration in obese mice and LPS-induced chronic inflammation mouse model. The data suggest that the interaction between gut microbiota and the immune system contributes to obesity-associated skeletal deterioration, and targeting senescent macrophages and GCA shows potential of protecting skeletal health in obese population.

Obesity is one of the important challenges to public health worldwide. Dysbiotic intestinal microbiota is a key factor in the onset and progression of obesity and related diseases. Short chain fatty acids (SCFAs) derived from butyricogenic bacteria has beneficial effects on obesity. Clostridium Butyricum 337279 (C.B), one of the SCFA producing bacteria, has been used to treat inflammatory bowel disease. The effect of C.B on obese mice remains unclear.

A high fat diet (HFD)-induced mouse model of obesity was constructed, and the mice were treated with C.B to examine their role on obesity and related metabolic disorder. RT-qPCR, Western blotting, immunohistochemical staining, and 16S rRNA gene sequencing were performed to investigate the role and mechanism of C.B. Plasma levels of BCAA and BCKA were detected by Shimadzu LC-20 AD liquid chromatography (LC) system.

Here we demonstrated that oral administration of C.B effectively alleviated HFD-induced obesity and associated metabolic disorders, including glucose intolerance and hyperlipidemia, as well as systemic inflammation, as evidenced by reduced levels of LPS, TNF-α, and IL-1β. C.B alleviated intestinal flora imbalance and modulated the composition of gut microbiota and their metabolites in HFD-induced obese mice. It also significantly ameliorated intestinal barrier disorders by increasing protein level of tight junction proteins ZO-1 and occludin. Importantly, dietary C.B potentially suppressed bacterial biosynthesis of branched-chain amino acids (BCAA) and reduced the excessive accumulation of BCAA in plasma, suggesting its role in restoring BCAA metabolism of mice.

C.B intervention significantly ameliorated gut microbiota imbalance in obese mice and alleviated obesity-related metabolic disorders by upregulating the expression of tight junction proteins (ZO-1 and occludin), attenuating endotoxemia and systemic inflammation and reducing microbial-derived BCAA production.

There is growing concern about the concept that exposure to environmental chemicals may be contributing to the obesity epidemic. However, there is no consensus on the obesogenic effects of emerging contaminants from a toxicological and environmental perspective. The potential human exposure and experimental evidence for obesogenic effects of emerging contaminants need to be systematically discussed. The main objective of this review is to provide recommendations for further subsequent policy development following a critical analysis of the literature for humans and experimental animals exposed to emerging contaminants. This article reviews human exposure to emerging contaminants (with a focus on antimicrobials, preservatives, water and oil repellents, flame retardants, antibiotics and bisphenols) and the impact of emerging contaminants on obesity. These emerging contaminants have been widely detected in human biological samples. Epidemiological studies provide evidence linking exposure to emerging contaminants to the risks of obesity in humans. Studies based on animal models and adipose cells show the obesogenic effects of emerging contaminants and identify modes of action by which contaminants may induce changes in body fat accumulation and lipid metabolic homeostasis. Some knowledge gaps in this area and future directions for further investigation are discussed.

The influence of gut microbiota on Type 2 Diabetes Mellitus (T2DM) is an emerging area of research. This review investigates the relationship between gut microbiota dysbiosis, bacterial translocation, and T2DM. It aims to elucidate how microbial imbalances contribute to the progression of T2DM through bacterial translocation and to evaluate dietary and therapeutic strategies to manage these effects.

Recent studies highlight that dysbiosis in T2DM patients often leads to increased systemic inflammation, impaired glucose metabolism, and disrupted gut barrier integrity. These disruptions promote elevated levels of harmful bacterial components, such as lipopolysaccharides, in the bloodstream. This, in turn, is linked to worsening insulin resistance and metabolic dysfunction. Advances in molecular methods and biomarkers have provided deeper insights into bacterial translocation and its impact on diabetes. Dietary interventions, including nutraceutical agents, high-fiber and low-glycemic index diets, as well as the use of probiotics and prebiotics, have shown promise in restoring gut health and mitigating bacterial translocation.

Maintaining a balanced gut microbiota and intestinal barrier integrity is crucial for managing T2DM. Therapeutic strategies, including dietary modifications and nutraceuticals, have demonstrated potential in reducing bacterial translocation and systemic inflammation. Continued research is needed to refine these approaches and explore novel treatment modalities for improving metabolic health in T2DM patients.

Type 2 diabetes mellitus (T2DM) is the third most common chronic metabolic disorder worldwide and seriously dangerous. Novel therapeutics are sought due to the paucity of safe and effective metabolic disorder-related diabetes medicines. Intestinal flora impacts glucose and lipid balance, making it a unique T2DM therapeutic target. Due to gut fermentation, poly/oligo-saccharides are highly beneficial prebiotic carbohydrates for intestinal health. Moreover, supplementation with naturally occurring medicinal and edible homologous traditional Chinese medicines (MEHTCM) poly/oligo-saccharides has significant antidiabetic effects with few side effects. Now, a comprehensive review of research developments of MEHTCM poly/oligo-saccharides was presented to explore their prospects. We outlined the structural characteristics, structure classification, and structure-activity relationships. Notably, structure-activity relationships illustrated that molecular weight, monosaccharide composition, and glycosidic bond type could influence the hypoglycemic activity and prebiotic effect of MEHTCM poly/oligo-saccharides. Additionally, the review systematically summarized the effect and potential mechanism of MEHTCM poly/oligo-saccharide on T2DM, focusing on gut microbiota. The potential applications in formulations for special medical purposes, common food, health care product, agriculture and other fields have also been summarized. This review emphasizes MEHTCM poly/oligo-saccharides' potential as prebiotics for T2DM treatment. This information provides new insights and a theoretical foundation for MEHTCM poly/oligo-saccharide nutritional and medicinal research.

Moringa oleifera Lamarck seeds (MOS) have been traditionally used in folk medicine and documented for their potential to alleviate type 2 diabetes symptoms, but the potential mechanisms are still unknown. The purpose of this article is to investigate the effects of MSAP (alkali-extracted polysaccharide from MOS) on diabetic rats by assessing its impact on the gut microbiome, diabetes-related biochemical markers, and fecal metabolomics. The results demonstrated that the fasting blood glucose, glucose tolerance, insulin resistance, insulin level and lipopolysaccharides (LPS) level in the rats treated with MSAP were all improved. Specifically, MSAP was found to modulate the composition and diversity of the gut microbiota, increasing the ratio of Firmicutes/Bacteroidetes, which enhanced the quantity of probiotic Lactobacillus and butyrate-producing bacteria, such as Roseburia, thereby reinforcing the intestinal epithelial barrier. Furthermore, fecal metabolomics indicates that MSAP actively regulates pathways closely associated with diabetes, including sphingolipid metabolism, amino acid synthesis and catabolism, retrograde endogenous cannabinoid signaling, and the modulation of TRP channels by inflammatory mediators. By integrating microbiome and metabolomics data, this study elucidated the mechanisms through which MSAP alleviates diabetes. In conclusion, the findings suggest that polysaccharides from MOS hold potential as a medicinal and edible homologous food for diabetes management.

Background/Objectives: The aim of this study was to qualitatively and quantitatively assess the bacterial domain of the gut microbiome in elderly patients with type 2 diabetes (T2D), with a focus on sex differences, glycemic control, and lipid disorders. Methods: This study included 60 older adults with T2D (38 women and 22 men) treated with metformin or a combination of metformin and insulin. The gut microbiota was profiled using 16S rRNA gene sequencing. Statistical analyses, including correlation analysis and multiple regression, were performed to identify the associations between microbial taxa, sex, and metabolic parameters. Results: No statistically significant differences in alpha or beta diversity were observed between the sexes. Multiple regression analysis indicated a positive relationship between Tenericutes and HbA1c in male participants (β = 2.22931, CI [0.75, 3.70], R = 0.67; R2 = 0.36; unadjusted p = 0.0052; adjusted p = 0.0496). In female participants, G0' (β = -2.24107, CI [-3.19, -1.30], R = 0.78; R2 = 0.58; unadjusted p = 0.00003; adjusted p = 0.0005) and HbA1c (β = -1.86670, CI [-2.61, -1.12], R = 0.78; R2 = 0.58; unadjusted p = 0.00001; adjusted p = 0.0003) correlated negatively with Verrucomicrobia as well G0' (β = -1.90427, CI [-2.95, -0.85], R = 0.46; R2 = 0.17; unadjusted p = 0.0008; adjusted p = 0.007) and HbA1c (β = -1.69561, CI [-2.52, -0.87], R = 0.46; R2 = 0.17; unadjusted p = 0.0002; adjusted p = 0.002) correlated negatively with OD1 bacteria, known as Parcubacteria. Conclusions: In this elderly population with type 2 diabetes, biological sex did not significantly affect the gut microbiota diversity. However, several exploratory associations between microbial taxa and metabolic parameters differed between men and women, suggesting that sex may influence specific aspects of microbiota-metabolism interactions. These preliminary findings underscore the importance of considering both age- and sex-related factors when investigating the gut microbiome in the context of type 2 diabetes.

In recent years, the gut microbiota and derived metabolites have emerged as relevant players in modulating several brain functions, including energy balance control1-3. This form of distant communication mirrors that of metabolic hormones (for example, leptin, ghrelin), which convey information about the organism's energy status by exerting effects on diverse brain regions, including the master homeostatic centre, the hypothalamus4. However, whether the hypothalamus is also able to influence gut microbiota composition remains enigmatic. Here we present a study designed to unravel this challenging question. To this aim, we used chemogenetics5 (to selectively activate or inhibit hypothalamic pro-opiomelanocortin or agouti-related peptide neurons) or centrally administered leptin or ghrelin to male mice. Subsequently, we conducted microbiota composition analysis throughout the gut using 16S rRNA gene sequencing. Our results showed that these brain interventions significantly changed the gut microbiota in an anatomical and short-term (2-4 h) fashion. Transcriptomic analysis indicated that these changes were associated with the reconfiguration of neuronal and synaptic pathways in the duodenum concomitant with increased sympathetic tone. Interestingly, diet-induced obesity attenuated the brain-mediated changes triggered by leptin in gut microbiota communities and sympathetic activation. Our findings reveal a previously unanticipated brain-gut axis that acutely attunes microbiota composition on fast timescales, with potential implications for meal-to-meal adjustments and systemic energy balance control.

The fern "Cyclosorus terminans" (C. terminans) or "Maiden Fern" contains interruptin A and interruptin B. This plant could attenuate obesity, insulin resistance, and fatty liver in rats fed a high-fat/calorie diet. However, the benefits of C. terminans to the gut remain unknown. We investigated the protective effect of C. terminans extract against gut dysfunction in rats exposed to a high-fat/calorie diet.

Male Wistar rats were assigned to receive either (1) a normal diet treated with vehicle, (2) a high-fat/calorie diet treated with vehicle, (3) a high-fat/calorie diet treated with 100 mg per kg per day (mg·kg-1·day-1) of C. terminans extract, or (4) a high-fat/calorie diet treated with 200 mg·kg-1·day-1 of C. terminans extract. The rats were euthanized after 12 weeks of treatment to enable feces and colon tissue collection.

Both 100 and 200 mg·kg-1·day-1 of C. terminans extract reduced body weight (-10.49%; p = 0.030 and -10.54%; p = 0.037, respectively) and ameliorated gut inflammation, gut barrier disruption, changes in short-chain fatty acid levels, and gut dysbiosis caused by high-fat/calorie diet.

C. terminans extract attenuated an increase in body weight and exerted prophylactic effects against gut pathologies induced by high-fat/calorie diet.

Obesity is a chronic metabolic disease, mainly caused by excessive/abnormal fat accumulation, as well as accompanied by endotoxemia and chronic inflammation. Quercetin, a natural flavonoid, may alleviate obesity by regulating gut microbiota and metabolites, but its exact mechanism for improving obesity is unknown.

The aim of this study was to investigate the effects of quercetin on high-fat diet (HFD)-induced obesity in mice. In particular, we focused on the regulatory effects of quercetin on gut microbiota and the tryptophan metabolite indole-3-propionic acid (IPA).

The C57BL/6J mice were subjected to a 20-week HFD feeding regimen with concurrent daily oral administration of quercetin or IPA. The body weight, fat accumulation, gut barrier function, and chronic inflammation were determined. Gut microbiota composition was analyzed by 16S rRNA sequencing and IPA levels were measured in serum and feces. In vitro experiments, Caco-2 cells were used to evaluate the effects of IPA and fecal dilutions from quercetin-treated mice on tight junction protein expression and aryl hydrocarbon receptor (AhR) activation.

Our results revealed that quercetin supplementation significantly mitigated obesity and chronic inflammation, and improved the disrupted gut barrier function through the actvation of AhR/interleukin 22 (IL-22) pathway. 16S rRNA sequencing revealed that quercetin treatment increased the abundance of Lactobacillus. Quercetin intervention increased the levels of IPA in the serum and feces of mice. IPA supplementation alleviated obesity and chronic inflammation, and enhanced intestinal barrier function through AhR activation. The findings were further corroborated by Caco-2 cell experiment, which indicated that the modulation of the dysregulated gut microbiota to change microbial metabolite IPA coordinated the improvement effect of quercetin on gut barrier disruption.

Quercetin supplementation alleviates obesity by restoring high-fat diet induced gut microbiota disorder, which elevates IPA level to activate AhR/IL-22 pathway, thereby enhancing intestinal barrier integrity and suppressing chronic inflammation.

The gut microbiome, a complex community of microorganisms residing in the intestinal tract, plays a dual role in colorectal cancer (CRC) development, acting both as a contributing risk factor and as a protective element. This review explores the mechanisms by which gut microbiota contribute to CRC, emphasizing inflammation, oxidative stress, immune evasion, and the production of genotoxins and microbial metabolites. Fusobacterium nucleatum, Escherichia coli (pks+), and Bacteroides fragilis promote tumorigenesis by inducing chronic inflammation, generating reactive oxygen species, and producing virulence factors that damage host DNA. These microorganisms can also evade the antitumor immune response by suppressing cytotoxic T cell activity and increasing regulatory T cell populations. Additionally, microbial-derived metabolites such as secondary bile acids and trimethylamine-N-oxide (TMAO) have been linked to carcinogenic processes. Conversely, protective microbiota, including Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii, contribute to intestinal homeostasis by producing short-chain fatty acids (SCFAs) like butyrate, which exhibit anti-inflammatory and anti-carcinogenic properties. These beneficial microbes enhance gut barrier integrity, modulate immune responses, and inhibit tumor cell proliferation. Understanding the dynamic interplay between pathogenic and protective microbiota is essential for developing microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, to prevent or treat CRC. Future research should focus on identifying microbial biomarkers for early CRC detection and exploring personalized microbiome-targeted therapies. A deeper understanding of host-microbiota interactions may lead to innovative strategies for CRC management and improved patient outcomes.

In this study, dietary exposures to 9 food emulsifiers, including 4 polysorbates and 5 esters of fatty acids, were assessed in Korean population. For the exposure assessment, three scenarios of the consumption, including mean and P95 in whole population and mean in consumed population, were applied. As a result, the EDIs of 9 emulsifiers were overall low compared to the ADIs. The total EDI to polysorbates was 1.72 % of the ADI in whole population. Exposures to polysorbate 20, 60, 65, and 80 were 0.02, 1.14, 0.39, and 0.29 % of the ADIs in whole population, respectively. Exposures to 5 esters of fatty acids were ranged from 0.57 to 6.13 % of the ADIs in whole population. In conclusion, it is considered that there are no safety concerns regarding the current consumption of the food emulsifiers. However, considering the change of food consumption, use levels, and health-based guidance values, periodic re-evaluation is necessary.

Previous observational studies have indicated a correlation between the skin microbiome and Type 2 diabetes (T2DM). It is hypothesized that this causal relationship may be influenced by inflammatory responses. However, these factors as determinants of T2DM remain largely unexplored.

This study incorporated data from the GWAS database on the skin microbiome, 91 types of inflammatory cytokines, and T2DM. We employed two-sample MR and multivariable MR methods to assess the correlation between the skin microbiome and T2DM, and to investigate whether this correlation is affected by inflammatory cytokines.

The results of the two-sample MR analysis indicate that within the skin microbiome, genetically predicted genus: Acinetobacter, class: Alphaproteobacteria, genus: Bacteroides, ASV005[Propionibacterium granulosum], and ASV072[Rothia mucilaginosa] are associated with an increased risk of T2DM, while phylum: Proteobacteria, genus: Enhydrobacter, family: Clostridiales, ASV006[Staphylococcus hominis] serve as protective factors against T2DM. Among the inflammatory cytokines, levels of Macrophage colony-stimulating factor 1, Tumor necrosis factor receptor superfamily member 9, Urokinase-type plasminogen activator, and C-C motif chemokine 28 are associated with an increased risk of T2DM. Multivariable MR analysis further revealed that Macrophage colony-stimulating factor 1 levels act as a mediating factor between ASV072[Rothia mucilaginosa] and T2DM.

In this study, we found a connection between the skin microbiome and T2DM, with inflammatory cytokines playing a key role in this relationship. This research helps us better understand this complex link and shows that addressing inflammation is important for preventing and treating diabetes. This could greatly benefit public health by reducing the impact of diabetes and its complications. Our results suggest that future studies should explore the specific biological interactions between the skin microbiome and diabetes to develop more effective risk management and treatment strategies from a microbial perspective.

Early-life antibiotic (ELA) exposure has garnered attention for its potential role in modulating obesity risk, although outcomes from mouse experiments and human epidemiological studies often vary based on dosage and sex. Low-dose (subtherapeutic) antibiotics can enhance energy availability through moderate alterations in gut microbiome profile, while high-dose (therapeutic) antibiotics substantially deplete the gut microbiota, thereby contributing to short-term negative energy balance. In this perspective, we propose a framework to understand how these distinct impacts of antibiotics on the gut microbiome during critical developmental windows shape long-term obesity risk through their influence on host energy balance. Using this framework, we then propose several hypotheses to explain variation in ELA-induced obesity outcomes across males and females. We conclude by discussing the evolutionary implications of ELAs, positing that the response of the gut microbiome to ELAs may signal energy availability and environmental volatility, influencing metabolic programming and adaptive traits across generations.

Recent studies have shown that Akkermansia muciniphila may play a role in regulating lipid metabolism and immune response in diet-induced obese mice. However, in contrast to diet-induced obesity, aging-related obesity is characterized by a gradual increase in body fat proportion over time. This type of obesity is thought to be caused by a combination of factors, including slow metabolism, unhealthy lifestyle choices, and chronic inflammation. Unlike diet-induced obesity, which can occur relatively quickly, aging-related obesity is a long-term and slow process. In this study, we administered Akkermansia muciniphila to aged mice and collected fecal samples to analyze the targeted metabolism of short chain fatty acids (SCFAs). The mice were then euthanized and their abdominal fat was weighed. hematoxylin-eosin (H&E) staining was performed to examine tissue samples. quantitative polymerase chain reaction (qPCR) was used to detect the expression of IL-6 and TNF-α. Flow cytometry was used to examine the proportion of lymphocytes. Enzyme-linked immunosorbent assays (ELISAs) kits were used to measure the levels of inflammatory factors and aging-related indicators. The results indicate that following intragastric administration, the body weight of the aged mice decreased, along with a decrease in abdominal fat and a reduction in the size of fat cells. Additionally, there was a decrease in the mRNA level of inflammatory factors, a decrease in the total number of immune cells in abdominal fat, and a decrease in the proportion of CD8+ CD4-cells. In addition, our findings showed that serum levels of IL-6, TNF-α, and lipopolysaccharide (LPS) were reduced, and catalase (CAT) and thyroid-stimulating hormone (TSH) levels were comparable to those of young mice. The findings revealed that Akkermansia muciniphila has the potential to enhance immune regulation in aged mice, alleviate persistent inflammation, and decrease obesity in this aged mice.

Adipose tissue is an immunologically active organ that controls host physiology, partly through the release of mediators termed adipokines. In obesity, adipocytes and infiltrating leukocytes produce adipokines, which include the hormones adiponectin and leptin and cytokines such as tumour necrosis factor and IL-1β. These adipokines orchestrate immune responses that are collectively referred to as metabolic inflammation. Consequently, metabolic inflammation characterizes metabolic disorders and promotes distinct disease aspects, such as insulin resistance, metabolic dysfunction-associated liver disease and cardiovascular complications. In this unifying concept, adipokines participate in the immunological cross-talk that occurs between metabolically active organs in metabolic diseases, highlighting the fundamental role of adipokines in obesity and their potential for therapeutic intervention. Here, we summarize how adipokines shape metabolic inflammation in mice and humans, focusing on their contribution to metabolic disorders in the setting of obesity and discussing their value as therapeutic targets.

This study aimed to evaluate if the intestinal permeability is associated with overweight/obesity with or without metabolic syndrome (MetS) and correlate intestinal permeability parameters with cardiovascular risk factors.

This was a cross-sectional study that individuals were divided in three groups: 1) controls (n = 34), 2) overweight/obesity (n = 29), and 3) overweight/obesity + MetS (n = 29). Anthropometric and blood biochemical parameters were used to estimate cardiovascular risk factors. Intestinal permeability was evaluated using the lactulose/mannitol test in urine samples analyzed by High Performance Liquid Chromatography with Pulsed Amperometry Detection. Correlations between intestinal permeability and anthropometric and biochemical parameters were evaluated using Spearman's correlations (r2). Logistic regression models were performed to elucidate variables associated with intestinal permeability parameters. The percentage of urinary excretion of lactulose, mannitol, and the lactulose/mannitol ratio was similar between the studied groups. The percentage of urinary mannitol excretion was positively associated with diastolic blood pressure (r2 = 0.24, p = 0.23), fasting glucose (r2 = 0.26, p = 0.013), fasting insulin (r2 = 0.25, p = 0.015) and HOMA-IR (r2 = 0.26, p = 0.012). The logistic regression showed fasting insulin was associated with a higher mannitol urinary excretion (AOR = 1.08, 95 % CI = 1.02-1.14).

Intestinal permeability was not disrupted in overweight/obesity and MetS, however the results suggest that the increased cardiovascular risk factors were associated with a higher intestinal absorption area. Further studies should investigate other intestinal parameters related to overweight/obesity and MetS in humans.