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.

Intestinal immunity is an important system for host defense and it is influenced by various factors such as diet and diseases. To elucidate the relationship between intestinal immunity and type 2 diabetes, we analyzed the effects of diabetes on intestinal antibody production and IgA repertoire using high-fat diet-fed mice and genetically diabetic KK-Ay mice model. The antibody level in the small intestine increased only in KK-Ay mice. We also confirmed that the IgA repertoire in both models experienced significant changes when compared to that in control mice, and no shared characteristics were observed between the two diabetic models. Antibody production in the intestine is influenced by stimuli associated with the onset of diabetes, and the types of induced IgA would differ depending on the process of disease onset.

Intestinal anastomosis is a critical procedure in both emergency and elective surgeries to maintain intestinal continuity. However, the incidence of anastomotic leakage (AL) has recently increased, reaching up to 20%, imposing major clinical and economic burdens. Substantial perioperative alterations in the intestinal microbiota composition may contribute to AL, particularly due to disruptions in key microbial populations essential for intestinal health and healing. The intricate interplay between the intestinal microbiota and the host immune system, along with microbial changes before and during surgery, significantly influences anastomotic integrity. Notably, specific pathogens such as Enterococcus and Pseudomonas aeruginosa have been implicated in AL pathogenesis. Preventive strategies including dietary regulation, personalized intestinal preparation, microbiota restoration and enhanced recovery after surgery protocols, may mitigate AL risks. Future research should focus on elucidating the precise mechanisms linking intestinal microbiota alterations to anastomotic healing and developing targeted interventions to improve surgical outcomes.

Obesity represents a chronic metabolic disorder feature by dysregulated glucose-lipid homeostasis. We investigated the effects of flaxseed oil (FO), rich in α-linolenic acid, and its blended oil (BO) on high-fat diet-induced obese mice. In the BO, the mass ratio of flaxseed oil, sunflower oil (as a source of linoleic acid), and olive oil (as a source of oleic acid) was precisely set at 11.90:51.64:36.46 (w/w/w) After 13 weeks of supplementation, both FO and BO significantly suppressed weight gain (multiple comparisons of weight gain on week 13: 8.57 ± 1.25 g in the ND group; 25.08 ± 2.96 g in the HFD group; 19.35 ± 1.47 g/19.71 ± 2.96 g in the HFD+FO/HFD+BO group), fat accumulation, and restored dyslipidemia (notably, FO administration resulted in a significant reduction in LDL-C and LEP levels (p < 0.01)), elevated blood glucose (FO demonstrated a more pronounced effect compared to BO), and liver tissue damage (specifically, FO exhibited a more pronounced effect in decreasing the levels of oxidative stress markers, including alanine aminotransferase (ALT) and malondialdehyde (MDA), and BO demonstrated greater efficacy in ameliorating the histopathological conditions of liver tissue) in HFD-fed mice. The 16S rRNA gene sequencing of mice fecal samples showed that FO and BO reduced the Firmicutes/Bacteroidetes (F/B) ratio (supplementation with FO decreased the F/B ratio from 68.95 to 15.24 (p < 0.01), while BO supplementation reduced it from 68.95 to 19.47), decreased the abundance of Proteobacteria (supplementation with FO decreased the abundance of Proteobacteria from 0.21 to 0.15, whereas supplementation with BO reduced it to 0.17). In addition, FO increased the abundance of Clostridium, and BO increased the abundance of Lactobacillus (rose from 5.42 to 10.3), reversing the imbalance of gut microbiota in obese mice. These findings suggest that FO and BO may be promising dietary strategies for treating obesity and improving its associated metabolic disorders.

Gastric cancer (GC) is one of the most common cancers worldwide particularly in Asian populations, and certain diets have been associated with increased risk of GC. Recent advances in microbial profiling technology have facilitated investigations on microbes residing on the gastric mucosa and increasing evidence has revealed the critical roles of non-Helicobacter pylori gastric microbes in gastric tumorigenesis. On the other hand, diets can affect microbial communities, causing compositional and functional shift of the microbiota. In this review, we summarize the influence of various diets including processed meat, salt-preserved food, high-fat diet, and alcohol on the development and progression of GC. We also explore microbial metabolites and host-microbe interactions in gastric tumorigenesis, alongside dietary interventions targeting the microbiota for the prevention and management against GC.

This study aimed to investigate the efficacy of polysaccharides from Artemisia sphaerocephala Krasch (ASK) seed in alleviating high fat diet (HFD) caused obesity. Here, three polysaccharide fractions (ASKP1, ASKP2 and ASKP3) were purified from ASK seed. Chemical characteristic analysis revealed that ASKP1 is a neutral heteropolysaccharide with the average molecular weight of 9.08 × 105 Da, while ASKP2 and ASKP3 are acidic heteropolysaccharides with the molecular weight of 9.39 × 105 and 8.41 × 105 Da, respectively. Animal experiment found that three ASKP fractions obviously relieved obesity and related metabolic disorders induced by HFD, while ASKP1 was more effective in reducing the blood glucose and serum LDL levels. 16S rDNA sequencing showed that ASKP fractions improved the gut microbiota imbalance of obese mice, and ASKP1 promoted the proliferation of beneficial bacterium Akkermansia more effectively than ASKP2 and ASKP3. Furthermore, ASKP fractions facilitated thermogenesis of brown adipose tissue (BAT) of obese mice, as evidenced by increased expression of thermogenic marker genes UCP1 in BAT, and the thermogenesis effect of ASKP1 was the most obvious. Taken together, our results show that ASKP1 is a novel prebiotic that may be used to treat obesity and its related abnormal metabolism.

Obesity is a growing global epidemic associated with changes in the gut microenvironment and metabolic endotoxemia, which can exacerbate metabolic and inflammatory processes. Citral (CT), a monoterpene present in essential oils, has been investigated for its anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in modulating the gut axis during metabolic and inflammatory alterations in obesity remains unknown. In this study, we investigated the effects of CT on intestinal and metabolic impairment induced by lipopolysaccharide (LPS) and high-fat diet (HFD) in in vitro and in vivo models.

Male C57BL/6J mice were fed a standard diet and HFD for 17 weeks, with daily oral administration of CT treatment (25, 100, or 300 mg/kg) or vehicle. Morphological and histological parameters, lipid profiles, adipose index, cytokine levels, and colonic gene expression were determined. In vitro, murine rectal carcinoma (CMT-93) cells were stimulated with LPS (10 μg/mL) to assess tight junction and inflammatory protein expression.

CT treatment showed anti-obesity activity against HFD-induced body mass gain in mice, which was attributed to a significant reduction in body fat, glycemia, and cholesterol levels. Systemic inflammation during obesity also decreased after CT treatment, with a significant reduction in serum levels of endotoxin, interleukin-1β, and tumor necrosis factor-α. Additionally, CT stimulation reduced inducible nitric oxide synthase expression and maintained ZO-1 levels in LPS-stimulated CMT-93 cells.

CT has anti-obesogenic, anti-inflammatory, and anti-hyperlipidemic properties mediated by its protective effects on the intestinal epithelium in obesity. Thus, our results highlight the promising preclinical results of CT treatment as a protective agent against the detrimental effects of HFD and LPS in mice.

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.

Lifestyle interventions, such as diet and exercise, are currently the main therapies against metabolic dysfunction-associated steatotic liver disease (MASLD). However, not much is known about the combined impact of fiber and exercise on the modulation of gut-liver axis and MASLD amelioration. Here, we studied the impact of the combination of exercise training and a fiber-rich diet on the amelioration of MASLD. Male APOE*3-Leiden.CETP mice were fed a high-fat high-cholesterol diet with or without the addition of fiber (10% inulin) and exercise trained on a treadmill, or remained sedentary. Exercise training and fiber supplementation reduced fat mass gain and lowered plasma glucose levels. Only the combination treatment, however, induced fat loss and decreased plasma triglyceride and cholesterol levels compared with sedentary control mice. Exercise training with and without the addition of fiber had a similar ameliorating effect on the MASLD score. Only exercise without fiber decreased the hepatic expression of inflammatory markers. Fiber diet was mainly responsible for remodeling the gut microbial composition, with an increase in the relative abundance of the short-chain fatty acid (SCFA)-producing genera Anaerostipes and Muribaculaceae, whereas, surprisingly, exercise training alone and with fiber resulted in the highest increase of SCFA production. Overall, the combination of exercise training and dietary fiber decreases fat mass and improves glucose and lipid homeostasis but does not have an additional synergistic positive effect on liver health compared with exercise training alone.NEW & NOTEWORTHY The combination of dietary fiber intake and exercise training has a synergetic beneficial effect on the metabolic health, resulting in fat loss, lowered blood glucose, and lowered plasma lipid levels in mice with steatotic liver disease. However, fiber supplementation, despite a positive remodulation of the gut-liver axis, does not have an additional positive effect on liver health compared with exercise training alone.

The vagus nerve is the body's primary sensory conduit from gut to brain, traditionally viewed as a passive relay for satiety signals. However, emerging evidence reveals a far more complex system-one that actively encodes diverse aspects of meal-related information, from mechanical stretch to nutrient content, metabolic state, and even microbial metabolites. This review challenges the view of vagal afferent neurons (VANs) as simple meal-termination sensors and highlights their specialized subpopulations, diverse sensory modalities, and downstream brain circuits, which shape feeding behavior, metabolism, and cognition. We integrate recent advances from single-cell transcriptomics, neural circuit mapping, and functional imaging to examine how VANs contribute to gut-brain communication beyond satiety, including their roles in food reward and memory formation. By synthesizing the latest research and highlighting emerging directions for the field, this review provides a comprehensive update on vagal sensory pathways and their role as integrators of meal information.

The purpose of this study was to evaluate the combined effects of puerarin (Pue) and insoluble dietary fiber from Hericium erinaceus (HEIDF) on obesity induced by a high-fat diet (HFD) in mice, focusing on their effects on lipid and glucose metabolism, gut microbiota (GM), and serum metabolites. Glucose tolerance, tissue pathology, and serum biochemical levels were conducted to assess the effects of puerarin combined with Hericium Erinaceus insoluble dietary fiber (LH) on glucose and lipid metabolism. 16S rRNA sequencing and untargeted metabonomics were employed to explore the underlying mechanisms. The results showed that the LH group significantly reduced body weight and hepatic and adipose lipid accumulation, and improved glucose tolerance and dyslipidemia compared to the Pue or HEIDF groups alone. Moreover, the LH group exhibited enhanced regulation of GM, including increased microbial diversity, higher abundance of beneficial bacteria such as g__Lactobacillus and g__Bacillus, and a decreased Firmicutes-to-Bacteroidota ratio. In addition, the LH group ameliorated HFD-induced serum metabolite changes and promoted the activation of tryptophan and glycerophospholipid metabolism pathways. The combination of Pue and HEIDF exhibits a synergistic anti-obesity effect by modulating specific GM (g__Lactobacillus and g__Bacillus) and serum metabolites.IMPORTANCEThe combination of HEIDF and Pue holds significant importance in the context of obesity. This synergistic effect not only aids in weight management but may also enhance metabolic health through various mechanisms, including increased satiety and promotion of fat oxidation. Therefore, incorporating these two components into the daily diet could offer effective strategies for the prevention and intervention of obesity and its related diseases.

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.

We have previously reported that dysregulated lipid metabolism and inflammation in 3T3-L1 adipocytes is attributed to tumor necrosis factor alpha (TNFα) rather than lipopolysaccharide (LPS) and palmitate (PA). In this study, we further compared the modulative effects of TNFα, LPS, and PA on mitochondrial function by treating 3T3-L1 adipocytes with TNFα (10 ng/mL), LPS (100 ng/mL), and PA (0.75 mM) individually or in combination for 24 h. Results showed a significant reduction in intracellular adenosine triphosphate (ATP) content, mitochondrial bioenergetics, total antioxidant capacity, and the mRNA expression of citrate synthase (Cs), sirtuin 3 (Sirt3), protein kinase AMP-activated catalytic subunit alpha 2 (Prkaa2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1α), nuclear respiratory factor 1 (Nrf1), and superoxide dismutase 1 (Sod1) in cells treated with TNFα individually or in combination with LPS and PA. Additionally, TNFα treatments decreased insulin receptor substrate 1 (Irs1), insulin receptor substrate 2 (Irs2), solute carrier family 2, facilitated glucose transporter member 4 (Slc2a4), and phosphoinositide 3 kinase regulatory subunit 1 (Pik3r1) mRNA expression. Treatment with LPS and PA alone, or in combination, did not affect the assessed metabolic parameters, while the combination of LPS and PA increased lipid peroxidation. These results show that TNFα but not LPS and PA dysregulate mitochondrial function, thus inducing oxidative stress and impaired insulin signaling in 3T3-L1 adipocytes. This suggests that TNFα treatment can be used as a basic in vitro model for studying the pathophysiology of mitochondrial dysfunction and related metabolic complications and screening potential anti-obesity therapeutics in 3T3-L1 adipocytes.

Colorectal cancer (CRC) is the third most common malignancy globally and the second leading cause of cancer-related mortality. Its development is a multifactorial and multistage process influenced by a dynamic interplay between gut microbiota, environmental factors, and fatty acid metabolism. Dysbiosis of intestinal microbiota and abnormalities in microbiota-associated metabolites have been implicated in colorectal carcinogenesis, highlighting the pivotal role of microbial and metabolic interactions. Fatty acid metabolism serves as a critical nexus linking dietary patterns with gut microbial activity, significantly impacting intestinal health. In CRC patients, reduced levels of short-chain fatty acids (SCFAs) and SCFA-producing bacteria have been consistently observed. Supplementation with SCFA-producing probiotics has demonstrated tumor-suppressive effects, while therapeutic strategies aimed at modulating SCFA levels have shown potential in enhancing the efficacy of radiation therapy and immunotherapy in both preclinical and clinical settings. This review explores the intricate relationship between gut microbiota, fatty acid metabolism, and CRC, offering insights into the underlying mechanisms and their potential translational applications. Understanding this interplay could pave the way for novel diagnostic, therapeutic, and preventive strategies in the management of CRC.

This study investigated the effect of oleogel consumption on lipid metabolism, gut microbiota and low-grade inflammation in rats fed with a high-fat diet. Male SD rats received either a control diet or high-fat diets for six weeks. The high-fat diets included a regular high-fat diet and high-fat diets in which lard was replaced with pure sunflower oil, un-gelled sunflower oil containing a dispersed gelator, or gelled sunflower oil with the gelator (oleogel). Results showed that compared to regular fat, pure sunflower oil and un-gelled sunflower oil consumption, oleogel consumption significantly suppressed weight gain and adipose tissue accumulation as well as serum and liver lipid accumulation. Microscopic observations further confirmed that oleogel intake alleviated white adipose tissue and liver steatosis caused by high-fat diet. Ex vivo biodistribution studies indicated an increased movement of TAGs toward the large intestine in the oleogel group. In the meantime, the dysregulation of gut microbiota was restored by reducing the Firmicutes/Bacteroidetes ratio and the relative abundance of Desulfobacterota and Proteobacteria. The oleogel group also exhibited reduced LPS levels in faeces, serum and liver. Furthermore, oleogel consumption alleviated inflammation, including decreased gene expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as suppressed protein expression of TLR4 and NF-κB in the liver. These results provide theoretical guidance for the regulation of oleogel properties and the potential application of oleogels as healthy fat replacers in high-fat diets.

Competitive exclusion is conventionally believed to prevent the establishment of a secondary strain of the same bacterial species in the gut microbiome, raising concerns for the deployment of live bacterial therapeutics (LBTs), especially if the bacterial chassis is a strain native to the gut. In this study, we investigated factors influencing competition dynamics in the murine gut using isogenic native Escherichia coli strains. We found that competition outcomes are context-dependent, modulated by microbiome complexity, LBT transgene expression, intestinal inflammation, and host diet. Furthermore, we demonstrated that native LBTs can establish long-term engraftment in the gut alongside a parental strain, with transgene-associated fitness effects influencing competition. We identified various interventions, including strategic dosing and dietary modulation, that significantly enhanced LBT colonization levels by 2 to 3 orders of magnitude. These insights provide a framework for optimizing LBT engraftment and efficacy, supporting their potential translation for human therapeutic applications.

Diet is one of the most important external factor shaping the composition and metabolic activities of the gut microbiome. The gut microbiome plays a crucial role in host health, including immune system development, nutrients metabolism, and the synthesis of bioactive molecules. In addition, the gut microbiome has been described as critical for the development of several mental disorders. Nutritional psychiatry is an emerging field of research that may provide a link between diet, microbial function, and brain health. In this study, we have reviewed the influence of different diet types, such as Western, Mediterranean, vegetarian, and ketogenic, on the gut microbiota composition and function, and their implication in various neuropsychiatric and psychological disorders.

Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.

Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1β mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.

This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet-induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet-induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short-chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome-based therapeutic strategies, it also investigates the effects of dietary components-fiber, polyphenols, and lipids-on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota-insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high-fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high-fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.

Edible fungi polysaccharides (EFPs) and gut microbiota (GM) play an important role in lipid metabolism. The structure of GM is complex and can be dynamically affected by the diet. EFPs can be used as dietary intervention to improve lipid metabolism directly, or by regulate the GM to participate in the host lipid metabolism by a complex mechanism. In this paper, we reviewed that EFPs regulate the balance of GM by increasing the number of beneficial bacteria and decreasing the number of harmful bacteria in the intestinal tract. The metabolites of GM are mainly bile acids (BAs), short-chain fatty acids (SCFAs), and lipopolysaccharides (LPS). EFPs can promote the synthesis of BAs and increase the content of SCFAs that produced by GM fermented EFPs, but reduce the content of LPS to regulate lipid metabolism. This review provides a valuable reference for further elucidation of the relationship between EFPs-GM-lipid metabolism and EFPs targeted regulation of GM to improve public health.

The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.

The considerable changes in lifestyle patterns primarily affect the human gut microbiota and result in obesity, diabetes, dyslipidemia, renal complications, etc. though there are few traditional safeguards such as herbal brews to maintain the ecological stability under intestinal dysbiosis. The present article is designed to collect all the scientific facts in a place to decipher the role of the Indian traditional herbal brews used to balance gut health for centuries. Computerized databases, commercial search engines, research papers, articles, and books were used to search by using different keywords to select the most appropriate published articles from 2000 onward to September 2023. A total of 1907 articles were scrutinized, 46 articles were finally selected from the 254 screened, and targeted information was compiled. Interaction of herbal brews to the gut microflora and resulting metabolites act as prebiotics due to antimicrobial, anti-inflammatory, and antioxidant properties, and modulate the pH of the gut. The effect of brews on gut microbiota has a drastic impact on various gut-related diseases and has gained popularity as an alternative to antibiotics against bacteria, fungi, viruses, parasites, and boosting the immune system and strengthening the intestinal barrier. Berberine, kaempferol, piperine, and quercetin have been found in more than one brew discussed in the present article. Practically, these brews balance the gut microbiota, prevent chronic and degenerative diseases, and reduce organ inflammation, though, there is a knowledge gap on the molecular mechanism to explain their efficacy. Indian traditional herbal brews used to reboot and heal the gut microbiota since centuries-old practice with successful history without toxicity. The systematic consumption of these brews under specific dietary prescriptions has a hope of arrays for a healthy human gut microbiome in the present hasty lifestyle with overall health and well-being.

Fructooligosaccharide (FOS) is a widely used prebiotic and health food ingredient, but few reports have focused on its risk to specific populations. Recently, it has been shown that the intake of inulin, whose main component is FOS, can lead to cholestasis and induce hepatocellular carcinoma in mice fed a high-fat diet (HFD); however, the molecular mechanism behind this is not clear. This study found that FOS supplementation induced abnormal enterohepatic circulation of bile acids in HFD-fed mice, which showed a significant increase in bile acid levels in the blood and liver, especially the secondary bile acids with high cytotoxicity, such as deoxycholic acid. The abundance of Clostridium, Bacteroides, and other bacteria in the gut microbiota also increased significantly. The analysis of the signaling pathway involved in regulating the enterohepatic circulation of bile acids showed that the weakening of the feedback inhibition of FXR-FGF15 and FXR-SHP signalling pathways possibly induced the enhancement of CYP7A1 activity and bile acid reabsorption in the blood and liver and led to an increase in bile acid synthesis and accumulation in the liver, increasing the risk of cholestasis. This study showed the risk of health damage caused by FOS supplementation in HFD-fed mice, which is caused by gut microbiota dysfunction and abnormal enterohepatic circulation of bile acids. Therefore, the application of FOS should be standardized to avoid the health risks of unreasonable FOS use in specific populations.

Background/Objective: Long-term intake of a high-fat diet (HFD) leads to obesity and gut dysbiosis. AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Herein, we investigated the impacts of Lactobacillus (Lactiplantibacillus) plantarum P111 and Bifidobacterium longum P121, which suppressed dexamethasone-induced adipogenesis in 3T3 L1 cells and increased lipopolysaccharide-suppressed AMPK activation in HepG2 cells, on HFD-induced obesity, liver steatosis, gut inflammation and dysbiosis, and depression/cognitive impairment (DCi)-like behavior in mice. Methods: Obesity is induced in mice by feeding with HFD. Biomarker levels were measured using immunoblotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Results: Orally administered P111, P121, or their mix LpBl decreased HFD-induced body weight gain, epididymal fat pad weight, and triglyceride (TG), total cholesterol (TC), and lipopolysaccharide levels in the blood. Additionally, they downregulated HFD-increased NF-κB activation and TNF-α expression in the liver and colon, while HFD-decreased AMPK activation was upregulated. They also suppressed HFD-induced DCi-like behavior and hippocampal NF-κB activation, NF-κB-positive cell population, and IL-1β and TNF-α levels, while increasing the hippocampal BDNF-positive cell population and BDNF level. The combination of P111 and P122 (LpBl) also improved body weight gain, liver steatosis, and DCi-like behavior. LpBl also mitigated HFD-induced gut dysbiosis: it decreased Desulfovibrionaceae, Helicobacteriaceae, Coriobacteriaceae, and Streptococcaceae populations and lipopolysaccharide production, which were positively correlated with TNF-α expression; and increased Akkermansiaceae, Bifidobacteriaceae, and Prevotellaceae populations, which were positively correlated with the BDNF expression. Conclusions: P111 and/or P121 downregulated adipogenesis, gut dysbiosis, and NF-κB activation and upregulatde AMPK activation, leading to the alleviation of obesity, liver steatosis, and DCi.

Our study was designed to investigate the Lactiplantibacillus plantarum 1008 (LP1008) on testicular antioxidant capacity, spermatogenesis, apoptosis, autophagy, and metabolic function in male mice with high-fat-diet-induced obesity. A total of thirty-six male C57BL/6 mice were fed a normal diet (denoted as the NC group) or a high-fat control diet (denoted as the HFC group) for 16 weeks, then half of the HFC group was randomly chosen and subsequently fed with LP1008 for the final 8 weeks (high-fat diet + LP1008; denoted as the HFP group). The HFP group expressed improved blood cholesterol, insulin resistance, hepatic function, and lipopolysaccharide (LPS) levels compared to the HFC group. Meanwhile, the HFC group displayed decreased testicular testosterone levels, sperm quality, and 17β-HSD protein expression, which were rescued after LP1008 treatment. Moreover, the HFC group had lower superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) enzyme activities. After LP1008 treatment, enhanced antioxidative activities and decreased lipid peroxidation were observed. The HFC group also exhibited aggravated apoptosis, inflammation, and autophagy proteins in the testis, which were ameliorated by LP1008 supplementation. Furthermore, the gut microbiota analysis results revealed that the Firmicutes/Bacteroidetes ratio was significantly elevated in the HFC and HFP groups compared to the NC group and that LP1008 treatment diminished Ruminococcaceae and enhanced Bifidobacteriaceae diversity. In summary, LP1008 treatment strengthened antioxidative enzyme levels and regulated microbiota-ameliorated HFC-induced oxidative stress, apoptosis, inflammation, and autophagy, and thus improved testicular function and semen quality.

The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.

Environmental insults during early development heavily affect brain trajectories. Among these, maternal infections, high-fat diet regimens, and sleep disturbances pose a significant risk for neurodevelopmental derangements in the offspring. Notably, scattered evidence is starting to emerge that also paternal lifestyle habits may impact the offspring development. Given their key role in controlling neurogenesis, synaptogenesis and shaping neuronal circuits, microglia represent the most likely suspects of mediating the detrimental effects of prenatal insults. For some of these environmental triggers, like maternal infections, ample literature evidence demonstrates the central role of microglia, also delineating the specific transcriptomic and proteomic profiles induced by these insults. In other contexts, the analysis of microglia is still in its infancy. Fostering these studies is needed to define microglia as potential therapeutic target in the frame of disorders consequent to maternal immune activation.

The global prevalence of obesity is rising year by year, which has become a public health problem worldwide. Many animal and clinical studies have shown that Lactiplantibacillus plantarum is considered an ideal probiotic and potential supplement for the treatment of obesity. In this study, we aimed to complete the genome sequence of L. plantarum HOM2217, which was isolated from human milk, and study its physiological characteristics and anti-obesity effects in 3T3-L1 cells and rats fed a high-fat diet (HFD) to determine its potential as a starter for functional food products. Whole-genome analysis demonstrated that HOM2217 contained a single circular chromosome of 3,267,529 bp with a GC content of 44.5% and one plasmid (62,350 bp) with a GC content of 38.5%. Compared to the reference strains, HOM2217 demonstrated superior tolerance to gastrointestinal conditions, higher adhesion to intestinal epithelial cell lines, potent antimicrobial activity against Enterobacter cloacae ATCC 13047, and effective cholesterol removal ability in vitro. Treatment with heat-killed HOM2217 significantly reduced lipid accumulation and intracellular triglyceride production in 3T3-L1 adipocytes. Daily treatment of HFD-fed rats with HOM2217 for 7 weeks decreased body weight, body weight gain, and body fat without changes in food intake. HOM2217 also significantly increased the serum high-density lipoprotein cholesterol (HDL-C) level, decreased the serum tumor necrosis factor (TNF-α) and increased short-chain fatty acid (SCFA) (formic acid, acetic acid, and butyric acid) levels in the cecum. Thus, HOM2217 could potentially prevent obesity in rats by inhibiting inflammatory responses and regulating lipid metabolism and SCFAs expression. Therefore, HOM2217 has potential as an alternative treatment for obesity.

Several studies indicate a strong link between obesity and the risk of breast cancer. Obesity decreases gut microbial biodiversity and modulates Bacteroidetes-to-Firmicutes phyla proportional abundance, suggesting that increased energy-harvesting capacity from indigestible dietary fibers and elevated lipopolysaccharide bioavailability may promote inflammation. To address the limited evidence linking diet-mediated changes in gut microbiota to breast cancer risk, we aimed to determine how diet affects the microbiome and breast cancer risk. For ten weeks, female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut oil, lard + flaxseed oil, and lard + safflower oil). Fecal 16S sequencing was performed for each group. Diet shifted fecal microbiome populations and modulated mammary gland macrophage infiltration. Fecal-conditioned media shifted macrophage polarity and inflammation. In our DMBA-induced breast cancer model, diet differentially modulated tumor and mammary gland metabolism. We demonstrated how dietary patterns change metabolic outcomes and the gut microbiota, possibly contributing to breast tumor risk. Furthermore, we showed the influence of diet on metabolism, inflammation, and macrophage polarity. This study suggests that dietary-microbiome interactions are key mediators of breast cancer risk. Prevention Relevance: Our study demonstrates the impact of diet on breast cancer risk, focusing on the interplay between diet, the gut microbiome, and mammary gland inflammation.

The characteristics of dairy products, such as texture, color, flavor, and nutritional profile, are significantly influenced by the presence of milk fat. However, saturated fatty acids account for 65% of total milk fat. With increased health awareness and regulatory recommendations, consumer preferences have evolved toward low/no saturated fat food products. Reducing the saturated fat content of dairy products to meet market demands is an urgent yet challenging task, as it may compromise product quality and increase production costs. In this regard, oleogels have emerged as a viable milk fat replacement in dairy foods. This review focuses on recent advances in oleogel systems and explores their potential for incorporation into dairy products as a milk fat substitute. Overall, it can be concluded that oleogel can be a potential alternative to replace milk fat fully or partially in the product matrix to improve nutritional profile by mimicking similar rheological and textural product characteristics as milk fat. Furthermore, the impact of consuming oleogel-based dairy foods on digestibility and gut health is also discussed. A thorough comprehension of the application of oleogels in dairy products will provide an opportunity for the dairy sector to develop applications that will appeal to the changing consumer needs.

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations. While CHIP is typically asymptomatic, it has garnered substantial attention due to its association with the pathogenesis of multiple disease conditions, including cardiovascular disease (CVD) and hematological malignancies. In this Review, we will discuss seminal and recent studies that have advanced our understanding of mechanisms that drive selection for mutant HSPCs in the BM niche. Next, we will address recent studies evaluating potential relationships between the clonal dynamics of CHIP and hematopoietic development across the lifespan. Next, we will examine the roles of systemic factors that can influence hematopoietic stem cell (HSC) fitness, including inflammation, and exposures to cytotoxic agents in driving selection for CHIP clones. Furthermore, we will consider how - through their impact on the BM niche - lifestyle factors, including diet, exercise, and psychosocial stressors, might contribute to the process of somatic evolution in the BM that culminates in CHIP. Finally, we will review the role of old age as a major driver of selection in CHIP.

Adipose tissue dysfunction, which is associated with an increased risk of colorectal cancer (CRC), is a significant factor in the pathophysiology of obesity. Obesity-related inflammation and extracellular matrix (ECM) remodeling promote colorectal cancer metastasis (CRCM) by shaping the tumor microenvironment (TME). When CRC occurs, the metabolic symbiosis of tumor cells recruits adjacent adipocytes into the TME to supply energy. Meanwhile, abundant immune cells, from adipose tissue and blood, are recruited into the TME, which is stimulated by pro-inflammatory factors and triggers a chronic local pro-inflammatory TME. Dysregulated ECM proteins and cell surface adhesion molecules enhance ECM remodeling and further increase contractibility between tumor and stromal cells, which promotes epithelial-mesenchymal transition (EMT). EMT increases tumor migration and invasion into surrounding tissues or vessels and accelerates CRCM. Colorectal symbiotic microbiota also plays an important role in the promotion of CRCM. In this review, we provide adipose tissue and its contributions to CRC, with a special emphasis on the role of adipocytes, macrophages, neutrophils, T cells, ECM, and symbiotic gut microbiota in the progression of CRC and their contributions to the CRC microenvironment. We highlight the interactions between adipocytes and tumor cells, and potential therapeutic approaches to target these interactions.

Obesity, as a global health crisis, is increasingly linked to intestinal microecology. Probiotics colonise the body, effectively regulating the balance of intestinal flora, while strengthening the intestinal barrier, activating the immune response, releasing beneficial substances, and maintaining micro-ecological balance. This process not only enhances the defence against pathogens, but also reduces the production of inflammatory factors and lowers the level of chronic inflammation. However, the specific process and mechanism by which probiotics influence the intestinal microecology through the immune response, improve metabolic disorders caused by obesity, and participate in weight management are not clear. Through multiple neural pathways including the 'gut-brain axis' and their direct interaction with the intestine, probiotics increase the number of beneficial bacteria in the intestine and inhibit the growth of harmful bacteria, thus effectively restructuring the balance of the intestinal flora. This restructuring of the balance can optimise the intestinal environment and enhance the efficiency of food digestion and nutrient absorption. Probiotics show positive effects on obesity management by regulating the metabolic process and reducing fat accumulation, providing individuals with a new way to control body weight and prevent obesity. Therefore, the application of probiotics is of great significance in promoting gut health and weight management.

The enteric nervous system (ENS) commands moment-to-moment gut functions through integrative neurocircuitry housed in the gut wall. The functional continuity of ENS networks is disrupted in enteric neuropathies and contributes to major disturbances in normal gut activities including abnormal gut motility, secretions, pain, immune dysregulation, and disrupted signaling along the gut-brain axis. The conditions under which enteric neuropathy occurs are diverse and the mechanistic underpinnings are incompletely understood. The purpose of this brief review is to summarize the current understanding of the cell types involved, the conditions in which neuropathy occurs, and the mechanisms implicated in enteric neuropathy such as oxidative stress, toll like receptor signaling, purines, and pre-programmed cell death.

The human gastrointestinal ecosystem, or microbiome (comprising the total bacterial genome in an environment), plays a crucial role in influencing host physiology, immune function, metabolism, and the gut-brain axis. While bacteria, fungi, viruses, and archaea are all present in the gastrointestinal ecosystem, research on the human microbiome has predominantly focused on the bacterial component. The colonization of the human intestine by microbes during the first two years of life significantly impacts subsequent composition and diversity, influencing immune system development and long-term health. Early-life exposure to pathogens is crucial for establishing immunological memory and acquired immunity. Factors such as maternal health habits, delivery mode, and breastfeeding duration contribute to gut dysbiosis. Despite fungi's critical role in health, particularly for vulnerable newborns, research on the gut mycobiome in infants and children remains limited. Understanding early-life factors shaping the gut mycobiome and its interactions with other microbial communities is a significant research challenge. This review explores potential factors influencing the gut mycobiome, microbial kingdom interactions, and their connections to health outcomes from childhood to adulthood. We identify gaps in current knowledge and propose future research directions in this complex field.

Lipopolysaccharides (LPS) present in the intestine are suggested to enter the bloodstream after consumption of high-fat diets and cause systemic inflammation and metabolic dysregulation through a process named "metabolic endotoxemia." This study aimed to determine the role of orally administered LPS to mice in the early stage of chronic low-grade inflammation induced by diet.

We supplemented the drinking water with E. coli derived LPS to mice fed either high-fat Western-style diet (WSD) or standard chow (SC) for 7 weeks (n = 16-17). Body weight was recorded weekly. Systemic inflammatory status was assessed by in vivo imaging of NF-κB activity at different time points, and glucose dysregulation was assessed by insulin sensitivity test and glucose tolerance test near the end of the study. Systemic LPS exposure was estimated indirectly via quantification of LPS-binding protein (LBP) and antibodies against LPS in plasma, and directly using an LPS-sensitive cell reporter assay.

Our results demonstrate that weight development and glucose regulation are not affected by LPS. We observed a transient LPS dependent upregulation of NF-κB activity in the liver region in both diet groups, a response that disappeared within the first week of LPS administration and remained low during the rest of the study. However, WSD fed mice had overall a higher NF-κB activity compared to SC fed mice at all time points independent of LPS administration. Our findings indicate that orally administered LPS has limited to no impact on systemic inflammation and metabolic dysregulation in mice fed a high-fat western diet and we question the capability of intestinally derived LPS to initiate systemic inflammation through a healthy and uncompromised intestine, even when exposed to a high-fat diet.

Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

Sleeplessness (insomnia) is a potential symptom of depression. A probiotic NVP1704 alleviates depression-like behavior and neuroinflammation in mice. Therefore, to understand whether NVP1704 could be effective against sleeplessness in vivo, we exposed immobilization stress (IS) in mice, then orally administered NVP1704 for 5 days, and assayed depression/anxiety-like behavior in the open field, elevated plus maze, and tail suspension tests, sleeping latency time, and sleep duration, euthanized then by exposure to CO2, and analyzed their related biomarkers. Oral administration of NVP1704 decreased IS-induced depression/anxiety-like behavior and sleeping latency time and increased IS-suppressed sleeping duration. NVP1704 increased IS-suppressed expression of γ-aminobutyric acid (GABA), GABAA receptor α1 (GABAARα1) and α2 subunits (GABAARα2), serotonin, 5-HT receptors (5-HT1AR and 5-HT1BR), and melatonin receptors (MT1R and MT2R) in the prefrontal cortex and thalamus. NVP1704 also increased the IS-suppressed GABAARα1-positive cell population in the prefrontal cortex and decreased IS-induced corticosterone, TNF-α, and IL-6 expression and the NF-κB+Iba1+ cell population in the brain and myeloperoxidase, TNF-α, and IL-6 expression and the NF-κB+CD11c+ cell population in the colon. Based on these findings, NVP1704 may alleviate depression/anxiety/sleeplessness-like behaviors through the upregulation of serotonergic and GABAergic systems and downregulation of NF-κB activation.

Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra-intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter-kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEVLPS) from complex biological samples, including faeces, plasma and the liver from lean and diet-induced obese (DIO) mice. bEVLPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super-resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage-specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation-related cytokines and their receptors (n = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEVLPS showed a higher abundance of Proteobacteria by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEVLPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (Il1rn, Ccr1, Cxcl10, Il2rg and Ccr2). Furthermore, a portion of bEVLPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well-established biological effects induced by gut bacteria on distant organs.