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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Diabetes is a global health issue affecting over 6% of the world and 11% of the US population. It is closely linked to insulin resistance, a pivotal factor in Type 2 diabetes development. This review explores a promising avenue for addressing insulin resistance through the lens of Milk-Derived Bioactive Peptides (MBAPs). Taken from casein or whey fractions of various milks, MBAPs exhibit diverse health-promoting properties. Specific interactions between these peptides and enzymes involved in glucose digestion and metabolism have been examined, leading to the identification of some key peptides exerting the effects. This review emphasizes the positive impact of MBAPs on glycemic control through various mechanisms. Different cell lines have been used to investigate MBAPs' effects on insulin signaling, inflammation, and oxidative stress. Preclinical in vivo studies have also shown that MBAPs lower glucose, stimulate insulin, and reduce inflammation. Human trials further substantiate these findings and suggest the potential utility of milk protein hydrolysates containing MBAPs in individuals with insulin resistance or T2D to improve insulin action and glucose homeostasis.

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.

Aging is associated with immune senescence and gut dysbiosis, both of which are heavily influenced by the diet. In this review, we summarize current knowledge regarding the impact of diets high in fiber, protein, or fat, as well as different dietary components (tryptophan, omega-3 fatty acids, and galacto-oligosaccharides) on the immune system and the gut microbiome in aging. Additionally, this review discusses how aging alters tryptophan metabolism, contributing to changes in immune function and the gut microbiome. Understanding the relationship between diet, the gut microbiome, and immune function in the context of aging is critical to formulate sound dietary recommendations for older individuals, and these personalized nutritional practices will ultimately improve the health and longevity of the elderly.

The microbiota, a complex assembly of microorganisms residing in various body systems, including the gastrointestinal tract, plays a crucial role in influencing various physiological processes in the human body. The dynamic nature of gut microbiota is especially pronounced in children and is influenced by factors like breastfeeding and antibiotic use. Dysbiosis, characterized by alterations in microbiota composition or function, is associated with several pediatric endocrine disorders, such as precocious puberty, polycystic ovarian syndrome, and diabetes mellitus. This review focuses on the intricate relationship between gut microbiota and the pediatric endocrine system. The aim of this narrative review is to critically examine the existing literature to elucidate the impact of gut microbiota on the pediatric endocrine system and associated disorders. Additionally, potential interventions, such as probiotics and current gaps in knowledge, will be discussed. Despite emerging treatments like probiotics, further research is needed to understand and validate their effectiveness in treating pediatric endocrine disorders associated with dysbiosis.

Background: Dietary fibre plays a crucial role in metabolic regulation, inflammation, and microbiome composition. However, its impact on systemic and oral health, particularly in periodontitis, remains unclear. This study investigated the effects of high- and low-fibre diets on body composition, glycaemic control, inflammation, microbiome, and metabolome in a murine model of experimental periodontitis. Methods: Thirty-six male C57BL/6 mice were randomised to a high-fibre (40% fibre) or low-fibre (5% fibre) diet for eight weeks. Body weight, fat mass, lean mass, fasting blood glucose, serum inflammatory markers, alveolar bone loss, and root length were assessed. Oral and faecal microbiome composition was analysed using 16S rRNA sequencing. Metabolomic and short-chain fatty acid (SCFA) profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). Results: Mice on the high-fibre diet exhibited significantly lower body weight (p < 0.0001), fat mass (p = 0.0007), and lean mass (p < 0.0001) compared to the low-fibre group. Fasting blood glucose levels were significantly lower in the high-fibre group (p = 0.0013). TNF-α and IFN-γ levels were significantly elevated in the low-fibre group (p < 0.0001), suggesting a heightened pro-inflammatory state. While alveolar bone loss and root length did not differ significantly, microbiome analysis revealed distinct bacterial compositions (PERMANOVA, p < 0.05), with fibre-fermenting taxa enriched in high-fibre-fed mice. Metabolomic analysis identified 19 significantly altered metabolites, indicating dietary adaptations. Conclusions: A high-fibre diet improves glycaemic control, reduces systemic inflammation, and alters microbial and metabolic profiles in experimental periodontitis. These findings highlight dietary fibre's role in modulating metabolic and inflammatory pathways relevant to periodontal and systemic diseases.

Yi Mai granule (YMG) is a traditional Chinese medicine (TCM) herbal decoction consisting of two TCM formulas: Gua-Lou-Ban-Xia decoction and Si-Jun-Zi decoction. YMG has shown clinical benefit in the treatment of nonalcoholic fatty liver disease (NAFLD), which may be due to its regulatory effects on lipid metabolism. Previous studies have highlighted the importance of the gut microbiota and its metabolites in the use of TCM. However, the effect of YMG on the gut microbiota in the treatment of NAFLD remains unclear. In this study, we established an NAFLD model in ApoE-/- mice and treated them with YMG. High-performance liquid chromatography was adopted to identify the chemical components of YMG. By mapping the candidate targets using network pharmacology, we found that the targets of the main components of YMG were significantly enriched in NAFLD-related pathways. Moreover, 16S rRNA gene sequencing revealed that YMG affected the constitution and metabolism of the gut microbiota in NAFLD model mice, including lipid and carbohydrate metabolism. Similarly, metabolites related to lipid and carbohydrate metabolism in mouse serum were significantly altered by YMG. The correlation heat map and network analyses showed that the gut microbiota and metabolites affected by YMG were closely related to the blood lipid content. Collectively, YMG may exert therapeutic effects by affecting the metabolism of gut microbiota, thus regulating lipid and carbohydrate metabolism. These findings offer novel insight into the pharmacological mechanism of YMG in the treatment of NAFLD and provide theoretical bases for its clinical applications.

The use of nonfood prebiotics, probiotics, and synbiotics has approximately tripled in the last 20 years. It is necessary to examine the associations of these substances with all-cause and cause-specific mortality in a large prospective cohort.

This study included 53,333 adults from the National Health and Nutrition Examination Survey 1999-2018. All participants answered questions on the use of dietary supplements and medications, including prebiotics, probiotics, and synbiotics. Death outcomes were determined by linkage to National Death Index records through 31 December 2019. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all causes, heart diseases, cancer, and other causes.

During a mean follow-up of 10.6 years, 9117 deaths were documented, including 2364 heart disease deaths, 1964 cancer deaths, and 4700 other causes deaths. Compared to nonusers, nonfood prebiotic, probiotic, and synbiotic users had a 59% (HR 0.41, 95% CI 0.30 to 0.56), 56% (HR 0.44, 95% CI 0.26 to 0.74), 49% (HR 0.51, 95% CI 0.31 to 0.83), and 64% (HR 0.36, 95% CI 0.23 to 0.59) for lower risk of all-cause, cancer, heart disease, and other causes mortality, respectively. Moreover, the inverse association of the use of prebiotics, probiotics, and synbiotics with mortality was stronger in female participants and participants without hypertension.

The use of nonfood prebiotics, probiotics, and synbiotics is significantly associated with lower all-cause mortality, as well as deaths from heart disease, cancer, and other causes.

Emerging evidence suggests a link between gut microbiota and intervertebral disc diseases (IDDs); however, the causal relationships remain unclear. This study aimed to evaluate the causal effects of gut microbiota on the risk of cervical disc disorders (CDD), other intervertebral disc disorders (OIDD), pyogenic intervertebral disc infections, and discitis, shedding light on the potential "gut-disc axis".

Genetic variation data for 202 gut microbiota taxa were obtained from the Dutch Microbiome Project, and disease outcome data were sourced from the FinnGen consortium. A Mendelian Randomization (MR) approach was employed to assess causal relationships, using genetic variants as instrumental variables. Sensitivity analyses, including tests for pleiotropy, heterogeneity, and reverse causation, ensured robust findings.

The study identified 20 gut microbial taxa with significant associations to IDDs. Notably, taxa within the Erysipelotrichaceae family showed consistent protective effects against OIDD after Bonferroni correction (P < 0.05). Associations between several species and specific diseases, such as Alistipes senegalensis with CDD and Ruminococcus lactaris with discitis, were also observed. Sensitivity analyses confirmed no evidence of confounding or reverse causation.

This study provides evidence of causal relationships between specific gut microbiota and IDDs, supporting the existence of a "gut-disc axis." The findings suggest that microbial dysbiosis may influence spinal health through systemic inflammation and immune regulation. These insights open new possibilities for microbiota-targeted interventions, such as probiotics or dietary modifications, to prevent or manage IDDs. However, further research is required to validate these therapeutic strategies.

One of the most prevalent urinary illnesses is kidney stone formation, often known as nephrolithiasis. The precise processes of kidney stone remain poorly known after substantial investigation. In order to successfully prevent and cure stone formation and recurrence, additional research into the pathophysiology of stone formation is of paramount importance. Ferroptosis is linked to a variety of renal diseases and is a critical factor in the death of cells. However, little is known about how ferroptosis-related genes (FRGs) contribute to the development of kidney stones.

The Ferroptosis Database and the Gene Expression Omnibus (GEO) database provided us with information on kidney stones and FRGs, respectively (FerrDb).

Eight DE-FRGs related to kidney stones were found in total, and they were all closely related to immune response and autophagy management. Following this, among the 8 DE-FRGs, LASSO and SVM-RFE algorithms chose FZD7, STK11, SUV39H1, and LCN2 as marker genes with suitable diagnostic capabilities. These marker genes may be involved in the control of the PPAR signaling pathway, mTOR signaling system, and fatty acid production of kidney stones, according to the functional enrichment analysis that followed. Additionally, 24 drugs that target two marker genes have been found. Despite this, the ceRNA networks have gained that the regulatory relationship between marker genes is rather complex. Additionally, the findings of the CIBERSORT investigation indicated that FZD7 and SUV39H1 may be linked to variations in the immune milieu of people who have kidney stones.

We developed a diagnostic tool and provided information on the development of kidney stones. In order to confirm its diagnostic applicability for kidney stones, more studies are needed before it may be used in clinical practice.

Botanical drugs and probiotic supplements present safer alternative options for the prevention and treatment of osteoporosis (OP). However, pathological disorders of the gut microbiota and the specific properties of probiotics and traditional Chinese medicine (TCM) significantly limit their therapeutic efficacy. Given the favorable synergistic and complementary effects between probiotics and herbal medicines, a creative combination of these approaches may address the issue of their current limited efficacy. A comprehensive analysis is necessary to provide a detailed review of their potential for combination, the mechanisms behind their synergy, scientific applications, and future developments. There exists a complex relationship between gut microbiota and OP, and the underlying regulatory mechanisms are multidimensional, involving the production of pro-inflammatory metabolites, immune system disruption, and the impairment of the intestinal mucosal barrier. Furthermore, we analyzed the complex mechanisms and potential connections between probiotics, TCM, and their combined applications. We highlighted the principle of complementary gain and the substantial therapeutic potential of their organic combination, which facilitates the release of active substances in TCM, increases the bioavailability of TCM, enhances probiotic delivery efficiency, and exerts synergistic effects. The combined use of probiotics and TCM offers a safe and effective strategy for managing OP and presents an innovative and promising direction for the future development of modern phytomedicine.

The gut microbiota-brain axis is a complex system that links the bacteria in our gut with our brain, it plays a part in what way we respond to stress. This chapter explores how stress affects the types of bacteria in the gut and shows the two-way connection between them. Stress can change the bacteria in our gut, which can cause various problems related to stress, like depression, anxiety, and irritable bowel syndrome (IBS). Figuring out how these interactions may help us develop new treatments that focus on the connection between gut bacteria and the brain. This chapter looks at how gut bacteria could help identify stress-related problems. It also discusses the difficulties and possibilities of using this research in medical practice. In the end, the chapter talks about what comes next in this quickly changing area. It highlights how important it is to include research about the gut-brain connection in overall public health plans.

Obesity is a major global concern and is generally attributed to a combination of genetic and environmental factors. Several hypotheses have been proposed to explain the evolutionary origins of obesity epidemic, including thrifty and drifty genotypes, and changes in thermogenesis. Here, we put forward the hypothesis of metaflammation, which proposes that due to intense selection pressures exerted by environmental pathogens, specific genes that help develop a robust defense mechanism against infectious diseases have had evolutionary advantages and that this may contribute to obesity in modern times due to connections between the immune and energy storage systems. Indeed, incorporating the genetic variations of gut microbiota into the complex genetic framework of obesity makes it more polygenic than previously believed. Thus, uncovering the evolutionary origins of obesity requires a multifaceted approach that considers the complexity of human history, the unique genetic makeup of different populations, and the influence of gut microbiome on host genetics.