Insights into the Anti-Adipogenic and Anti-Inflammatory Potentialities of Probiotics against Obesity.

Functional foods with probiotics are safe and effective dietary supplements to improve overweight and obesity. Thus, altering the intestinal microflora may be an effective approach for controlling or preventing obesity. This review aims to summarize the experimental method used to study probiotics and obesity, and recent advances in probiotics against obesity. In particular, we focused on studies (in vitro and in vivo) that used probiotics to treat obesity and its associated comorbidities. Several in vitro and in vivo (animal and human clinical) studies conducted with different bacterial species/strains have reported that probiotics promote anti-obesity effects by suppressing the differentiation of pre-adipocytes through immune cell activation, maintaining the Th1/Th2 cytokine balance, altering the intestinal microbiota composition, reducing the lipid profile, and regulating energy metabolism. Most studies on probiotics and obesity have shown that probiotics are responsible for a notable reduction in weight gain and body mass index. It also increases the levels of anti-inflammatory adipokines and decreases those of pro-inflammatory adipokines in the blood, which are responsible for the regulation of glucose and fatty acid breakdown. Furthermore, probiotics effectively increase insulin sensitivity and decrease systemic inflammation. Taken together, the intestinal microbiota profile found in overweight individuals can be modified by probiotic supplementation which can create a promising environment for weight loss along enhancing levels of adiponectin and decreasing leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-ß on human health.

A high-fat diet promotes cancer progression by inducing gut microbiota-mediated leucine production and PMN-MDSC differentiation.

A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.

Hypocholesterolemic potential of Bacillus amyloliquefaciens KAVK1 modulates lipid accumulation on 3T3-L1 adipose cells and high fat diet-induced obese rat model.

The significance of microorganisms occurring in foods is predominantly targeted due to their application for identifying a novel range of the bacterial spectrum. Diverse microbial species are capable of exhibiting potential pharmacological activities like antimicrobial and anticancer. Microbial strains capable of reducing obesity-related syndromes have also been reported. In the present study, the hypocholesterolemic efficacy of Bacillus amyloliquefaciens isolated from dairy products was scrutinised by in vitro (3T3-L1 adipose cells) and in vivo (high-fat diet-induced obese Wistar albino rats) methods. Potential cholesterol-lowering isolates were screened using a plate assay method and optimised by physical parameters. Molecular identification of the topmost five cholesterol-lowering isolates was acquired by amplification of the 16 S rRNA gene region. Bacillus amyloliquefaciens strain KAVK1, followed by strains KAVK2, KAVK3, KAVK4, and KAVK5 were molecularly determined. Further, cholesterol-lowering strains degraded the spectral patterns determined by the side chain of a cholesterol molecule. The anti-lipase activity was demonstrated using the porcine pancreatic lipase inhibitory method and compared with the reference compound Atorvastatin. Lyophilised strain KAVK1 revealed maximum pancreatic lipase inhibition. Strain KAVK1 attenuated lipid accumulation in 3T3-L1 adipose cell line predicted by Oil Red O staining method. Significant reduction of body weight and change in lipid profile was recognised after the supplement of KAVK1 to obese rats. Histopathological changes in organs were predominantly marked. The result of this study implies that the cholesterol-lowering B. amyloliquefaciens KAVK1 strain was used to treat hypercholesterolemia.

The Role of Prebiotics in Modulating Gut Microbiota: Implications for Human Health.

The human gut microbiota, an intricate ecosystem within the gastrointestinal tract, plays a pivotal role in health and disease. Prebiotics, non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of beneficial microorganisms, have emerged as a key modulator of this complex microbial community. This review article explores the evolution of the prebiotic concept, delineates various types of prebiotics, including fructans, galactooligosaccharides, xylooligosaccharides, chitooligosaccharides, lactulose, resistant starch, and polyphenols, and elucidates their impact on the gut microbiota composition. We delve into the mechanisms through which prebiotics exert their effects, particularly focusing on producing short-chain fatty acids and modulating the gut microbiota towards a health-promoting composition. The implications of prebiotics on human health are extensively reviewed, focusing on conditions such as obesity, inflammatory bowel disease, immune function, and mental health. The review further discusses the emerging concept of synbiotics-combinations of prebiotics and probiotics that synergistically enhance gut health-and highlights the market potential of prebiotics in response to a growing demand for functional foods. By consolidating current knowledge and identifying areas for future research, this review aims to enhance understanding of prebiotics' role in health and disease, underscoring their importance in maintaining a healthy gut microbiome and overall well-being.

Metabolic Interaction Between Host and the Gut Microbiota During High-Fat Diet-Induced Colorectal Cancer.

Colorectal cancer (CRC) is the second-highest cause of cancer-associated mortality among both men and women worldwide. One of the risk factors for CRC is obesity, which is correlated with a high-fat diet prevalent in Western dietary habits. The association between an obesogenic high-fat diet and CRC has been established for several decades; however, the mechanisms by which a high-fat diet increases the risk of CRC remain unclear. Recent studies indicate that gut microbiota strongly influence the pathogenesis of both high-fat diet-induced obesity and CRC. The gut microbiota is composed of hundreds of bacterial species, some of which are implicated in CRC. In particular, the expansion of facultative anaerobic Enterobacteriaceae, which is considered a microbial signature of intestinal microbiota functional imbalance (dysbiosis), is associated with both high-fat diet-induced obesity and CRC. Here, we review the interaction between the gut microbiome and its metabolic byproducts in the context of colorectal cancer (CRC) during high-fat diet-induced obesity. In addition, we will cover how a high-fat diet can drive the expansion of genotoxin-producing Escherichia coli by altering intestinal epithelial cell metabolism during gut inflammation conditions.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Alteration of Gut Microbiota Composition in the Progression of Liver Damage in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and ß-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.

Semaglutide alleviates gut microbiota dysbiosis induced by a high-fat diet.

This study investigated the effects of semaglutide (Sema) on the gut microbiota of obese mice induced with high-fat diet (HFD). Male C57BL/6 J mice aged 6 weeks were enrolled and randomly distributed to four groups, which were provided with a normal control diet (NCD,NCD + Sema) and a 60% proportion of a high-fat diet (HFD,HFD + Sema), respectively. HFD was given for 10 weeks to develop an obesity model and the intervention was lasted for 18 days. The results showed semaglutide significantly reduced body weight gain, areas under the curve (AUC) of glucose tolerance test and insulin resistance test, as well as adipose tissue weight in mice. Semaglutide effectively reduced lipid deposition and lipid droplet formation in the liver of obese mice, and regulated the expression of genes related to abnormal blood glucose regulation. Additionally, semaglutide influenced the composition of gut microbiota, mitigating the microbial dysbiosis induced by a high-fat diet by impacting the diversity of the gut microbiota. After the high-fat diet intervention, certain strains such as Akkermansia, Faecalibaculum, and Allobaculum were significantly decreased, while Lachnospiraceae and Bacteroides were significantly increased. However, the application of semaglutide restored the lost flora and suppressed excessive bacterial abundance. Moreover, semaglutide increased the content of tight junction proteins and repaired the damage to intestinal barrier function caused by the high-fat diet intervention. Furthermore, correlation analysis revealed inverse relationship among Akkermansia levels and weight gain, blood glucose levels, and various obesity indicators. Correlation analysis also showed that Akkermansia level was negatively correlated with weight gain, blood glucose levels and a range of obesity indicators. This phenomenon may explain the anti-obesity effect of semaglutide, which is linked to alterations in gut microbiota, specifically an increase in the abundance of Akkermansia. In summary, our findings indicate that semaglutide has the potential to alleviate gut microbiota dysbiosis, and the gut microbiota may contribute to the obesity-related effects of this drug.

Modulating a prebiotic food source influences inflammation and immune-regulating gut microbes and metabolites: insights from the BE GONE trial.

BACKGROUND: Accessible prebiotic foods hold strong potential to jointly target gut health and metabolic health in high-risk patients. The BE GONE trial targeted the gut microbiota of obese surveillance patients with a history of colorectal neoplasia through a straightforward bean intervention. METHODS: This low-risk, non-invasive dietary intervention trial was conducted at MD Anderson Cancer Center (Houston, TX, USA). Following a 4-week equilibration, patients were randomized to continue their usual diet without beans (control) or to add a daily cup of study beans to their usual diet (intervention) with immediate crossover at 8-weeks. Stool and fasting blood were collected every 4 weeks to assess the primary outcome of intra and inter-individual changes in the gut microbiome and in circulating markers and metabolites within 8 weeks. This study was registered on ClinicalTrials.gov as NCT02843425, recruitment is complete and long-term follow-up continues. FINDINGS: Of the 55 patients randomized by intervention sequence, 87% completed the 16-week trial, demonstrating an increase on-intervention in diversity [n = 48; linear mixed effect and 95% CI for inverse Simpson index: 0.16 (0.02, 0.30); p = 0.02] and shifts in multiple bacteria indicative of prebiotic efficacy, including increased Faecalibacterium, Eubacterium and Bifidobacterium (all p < 0.05). The circulating metabolome showed parallel shifts in nutrient and microbiome-derived metabolites, including increased pipecolic acid and decreased indole (all p < 0.002) that regressed upon returning to the usual diet. No significant changes were observed in circulating lipoproteins within 8 weeks; however, proteomic biomarkers of intestinal and systemic inflammatory response, fibroblast-growth factor-19 increased, and interleukin-10 receptor-α decreased (p = 0.01). INTERPRETATION: These findings underscore the prebiotic and potential therapeutic role of beans to enhance the gut microbiome and to regulate host markers associated with metabolic obesity and colorectal cancer, while further emphasizing the need for consistent and sustainable dietary adjustments in high-risk patients. FUNDING: This study was funded by the American Cancer Society.

Potential for Improvement of Gut Microbiota Deterioration Caused by a High-fat, High-sucrose Diet through Administration of Acylated Steryl-ß-glycosides.

Consumption of a high-fat diet (HFD) is associated with an increased risk of metabolic diseases, cancer, and neurological disorders, which are major global health concerns. In the present study, mice were fed a HFD containing 40% fat and 0.5% or 1.0% acylated steryl-ß-glucosides (ASG) and their gut microbiota was compared to that of mice fed with a low-fat diet (LFD). After 55 d, the epididymal fat weight was higher in the HFD and ASG groups than in the LFD group; however, the epididymal fat weight was lower in the ASG group than in the HFD group. The abundance of gut microbiota increased with HFD in obese micespecific Bacillota, but decreased when ASG was added to the HFD. The number of intestinal bacteria involved in the production of carcinogenic secondary bile acids was increased by the consumption of HFD, but decreased by the addition of ASG to HSD. This finding may indicate the gut bacteria-mediated health benefits of ASG.

Linking Migraine to Gut Dysbiosis and Chronic Non-Communicable Diseases.

In the world, migraine is one of the most common causes of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers in combination with a genetic predisposition. Among the factors related to migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this context, in addition to conventional pharmacological treatments for migraine, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity, and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, such as diabetes mellitus, arterial hypertension, obesity, cancer, and chronic kidney diseases, whose link is represented by gut dysbiosis.

Isoxanthohumol improves obesity and glucose metabolism via inhibiting intestinal lipid absorption with a bloom of Akkermansia muciniphila in mice.

OBJECTIVE: Polyphenols have health-promoting effects, such as improving insulin resistance. Isoxanthohumol (IX), a prenylated flavonoid found in beer hops, has been suggested to reduce obesity and insulin resistance; however, the mechanism remains unknown. METHODS: High-fat diet-fed mice were administered IX. We analyzed glucose metabolism, gene expression profiles and histology of liver, epididymal adipose tissue and colon. Lipase activity, fecal lipid profiles and plasma metabolomic analysis were assessed. Fecal 16s rRNA sequencing was obtained and selected bacterial species were used for in vitro studies. Fecal microbiota transplantation and monocolonization were conducted to antibiotic-treated or germ-free (GF) mice. RESULTS: The administration of IX lowered weight gain, decreased steatohepatitis and improved glucose metabolism. Mechanistically, IX inhibited pancreatic lipase activity and lipid absorption by decreasing the expression of the fatty acid transporter CD36 in the small intestine, which was confirmed by increased lipid excretion in feces. IX administration increased markers of intestinal barrier function, including thickening the mucin layer and increasing caludin-1, a tight-junction related protein in the colon. In contrast, the effects of IX were nullified by antibiotics. As revealed using 16S rRNA sequencing, the microbial community structure changed with a significant increase in the abundance of Akkermansia muciniphila in the IX-treated group. An anaerobic chamber study showed that IX selectively promoted the growth of A. muciniphila while exhibiting antimicrobial activity against some Bacteroides and Clostridium species. To further explore the direct effect of A. muciniphila on lipid and glucose metabolism, we monocolonized either A. muciniphila or Bacteroides thetaiotaomicron to GF mice. A. muciniphila monocolonization decreased CD36 expression in the jejunum and improved glucose metabolism, with decreased levels of multiple classes of fatty acids determined using plasma metabolomic analysis. CONCLUSIONS: Our study demonstrated that IX prevents obesity and enhances glucose metabolism by inhibiting dietary fat absorption. This mechanism is linked to suppressing pancreatic lipase activity and shifts in microbial composition, notably an increase in A. muciniphila. These highlight new treatment strategies for preventing metabolic syndrome by boosting the gut microbiota with food components.

A review on Impact of dietary interventions, drugs, and traditional herbal supplements on the gut microbiome.

The gut microbiome is the community of healthy, and infectious organisms in the gut and its interaction in the host gut intestine (GI) environment. The balance of microbial richness with beneficial microbes is very important to perform healthy body functions like digesting food, controlling metabolism, and precise immune function. Alternately, this microbial dysbiosis occurs due to changes in the physiochemical condition, substrate avidity, and drugs. Moreover, various categories of diet such as "plant-based", "animal-based", "western", "mediterranean", and various drugs (antibiotic and common drugs) also contribute to maintaining microbial flora inside the gut. The imbalance (dysbiosis) in the microbiota of the GI tract can cause several disorders (such as diabetes, obesity, cancer, inflammation, and so on). Recently, the major interest is to use prebiotic, probiotic, postbiotic, and herbal supplements to balance such microbial community in the GI tract. But, there has still a large gap in understanding the microbiome function, and its relation to the host diet, drugs, and herbal supplements to maintain the healthy life of the host. So, the present review is about the updates on the microbiome concerns related to diet, drug, and herbal supplements, and also gives research evidence to improve our daily habits regarding diet, drugs, and herbal supplements. Because our regular dietary plan and traditional herbal supplements can improve our health by balancing the bacteria in our gut.

Remodeling of the Gut Microbiota in Colorectal Cancer and its Association with Obesity.

The considerable burden of colorectal cancer and the increasing prevalence in young adults emphasizes the necessity of understanding its underlying mechanisms and risk factors as well as providing more effective treatments. There is growing evidence of a positive relationship between obesity and colorectal cancer. Furthermore, the prominent role of gut microbiota dysbiosis in colorectal carcinogenesis is becoming more evident. Sequencing studies demonstrate an altered composition and ecology of intestinal microorganisms in both colorectal cancer and obese patients and have pinpointed some specific bacteria as the key role players. The purpose of this review is to provide a general outlook of how gut microbiota may impact the initiation and promotion of colorectal cancer and describes probable links between gut microbiota and obesity. We also provide evidence about targeting the microbiota as an intervention strategy for both ameliorating the risk of cancer and augmenting the therapy efficacy.

Effect of Diets Varying in Iron and Saturated Fat on the Gut Microbiota and Intestinal Inflammation: A Crossover Feeding Study among Older Females with Obesity.

Obesity is considered an independent risk factor for colorectal cancer (CRC). Altered nutrient metabolism, particularly changes to digestion and intestinal absorption, may play an important role in the development of CRC. Iron can promote the formation of tissue-damaging and immune-modulating reactive oxygen species. We conducted a crossover, controlled feeding study to examine the effect of three, 3-week diets varying in iron and saturated fat content on the colonic milieu and systemic markers among older females with obesity. Anthropometrics, fasting venous blood and stool were collected before and after each diet. There was a minimum 3-week washout period between diets. Eighteen participants consumed the three diets (72% Black; mean age 60.4 years; mean body mass index 35.7 kg/m2). Results showed no effect of the diets on intestinal inflammation (fecal calprotectin) or circulating iron, inflammation, and metabolic markers. Pairwise comparisons revealed less community diversity between samples (beta diversity, calculated from 16S rRNA amplicon sequences) among participants when consuming a diet low in iron and high in saturated fat vs. when consuming a diet high in iron and saturated fat. More studies are needed to investigate if dietary iron represents a salient target for CRC prevention among individuals with obesity.

Anti-inflammatory mechanisms of polyphenols in adipose tissue: role of gut microbiota, intestinal barrier integrity and zinc homeostasis.

Obesity is associated with an imbalance of micro-and macro-nutrients, gut dysbiosis, and a "leaky" gut phenomenon. Polyphenols, such as curcumin, resveratrol, and anthocyanins may alleviate the systemic effects of obesity, potentially by improving gut microbiota, intestinal barrier integrity (IBI), and zinc homeostasis. The essential micronutrient zinc plays a crucial role in the regulation of enzymatic processes, including inflammation, maintenance of the microbial ecology, and intestinal barrier integrity. In this review, we focus on IBI- which prevents intestinal lipopolysaccharide (LPS) leakage - as a critical player in polyphenol-mediated protective effects against obesity-associated white adipose tissue (WAT) inflammation. This occurs through mechanisms that block the movement of the bacterial endotoxin LPS across the gut barrier. Available research suggests that polyphenols reduce WAT and systemic inflammation via crosstalk with inflammatory NF-κB, the mammalian target of rapamycin (mTOR) signaling and zinc homeostasis.

Walnut peptide alleviates obesity, inflammation and dyslipidemia in mice fed a high-fat diet by modulating the intestinal flora and metabolites.

Introduction: Obesity is a chronic disease in which the body stores excess energy in the form of fat, and intestinal bacterial metabolism and inflammatory host phenotypes influence the development of obesity. Walnut peptide (WP) is a small molecule biopeptide, and the mechanism of action of WP against metabolic disorders has not been fully elucidated. In this study, we explored the potential intervention mechanism of WP on high-fat diet (HFD)-induced obesity through bioinformatics combined with animal experiments. Methods: PPI networks of Amino acids and their metabolites in WP (AMWP) and "obesity" and "inflammation" diseases were searched and constructed by using the database, and their core targets were enriched and analyzed. Subsequently, Cytoscape software was used to construct the network diagram of the AMWP-core target-KEGG pathway and analyze the topological parameters. MOE2019.0102 was used to verify the molecular docking of core AMWP and core target. Subsequently, an obese Mice model induced by an HFD was established, and the effects of WP on obesity were verified by observing weight changes, glucose, and lipid metabolism levels, liver pathological changes, the size of adipocytes in groin adipose tissue, inflammatory infiltration of colon tissue, and intestinal microorganisms and their metabolites. Results: The network pharmacology and molecular docking showed that glutathione oxide may be the main active component of AMWP, and its main targets may be EGFR, NOS3, MMP2, PLG, PTGS2, AR. Animal experiments showed that WP could reduce weight gain and improve glucose-lipid metabolism in HFD-induced obesity model mice, attenuate hepatic lesions reduce the size of adipocytes in inguinal adipose tissue, and reduce the inflammatory infiltration in colonic tissue. In addition, the abundance and diversity of intestinal flora were remodeled, reducing the phylum Firmicutes/Bacteroidetes (F/B) ratio, while the intestinal mucosal barrier was repaired, altering the content of short-chain fatty acids (SCFAs), and alleviating intestinal inflammation in HFD-fed mice. These results suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism and anti-inflammation. Discussion: Our findings suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism, and exerting anti-inflammatory effects. Thus, WP may be a potential therapeutic strategy for preventing and treating metabolic diseases, and for alleviating the intestinal flora disorders induced by these diseases. This provides valuable insights for the development of WP therapies.

Altered Gut Microbial Profile Accompanied by Abnormal Fatty Acid Metabolism Activity Exacerbates Endometrial Cancer Progression.

Endometrial cancer (EC) is the most prevalent gynecological malignancy, with a higher risk in obese woman, indicating the possibility of gut microbiota involvement in EC progression. However, no direct evidence of a relationship between EC and gut microbiota in humans has been discovered. Here, we performed 16S rRNA sequencing to explore the relationship between dysbiosis of gut microbiota and cancer development in different types of EC patients. The results clearly show the differential profiles of gut microbiota between EC patients and normal participants as well as the association between gut microbiota and EC progression. Targeted metabolomics of plasma revealed an increased level of C16:1 and C20:2, which was positively associated with the abundance of Ruminococcus sp. N15.MGS-57. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects not only was positively associated with blood C16:1 and C20:2 but also was negatively correlated with betalain and indole alkaloid biosynthesis. Furthermore, the combined marker panel of gut bacteria, blood metabolites, and clinical indices could distinguish the EC patients under lean and overweight conditions from normal subjects with high accuracy in both discovery and validation sets. In addition, the alteration of tumor microenvironment metabolism of EC was characterized by imaging mass microscopy. Spatial visualization of fatty acids showed that C16:1 and C18:1 obviously accumulate in tumor tissue, and C16:1 may promote EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1 in EC tissues, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment. IMPORTANCE A growing number of studies have shown the connection between gut microbiota, obesity, and cancer. However, to our knowledge, the association between gut microbiota and endometrial cancer progression in humans has not been studied. We recruited EC and control individuals as research participants and further subgrouped subjects by body mass index to examine the association between gut microbiota, metabolites, and clinical indices. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects was not only positively associated with blood C16:1 but also negatively correlated with betalain and indole alkaloid biosynthesis. Spatial visualization of fatty acids by imaging mass microscopy showed that C16:1 obviously accumulates in tumor tissue, and C16:1 may promote the EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment.

Beneficial effects of fermented barley extracts on inflammatory status and gut microbiota in high-fat diet-induced obese rats.

AIMS: To explore how fermented barley extracts could affect obesity-associated inflammatory responses to ameliorate high-fat diet (HFD)-induced obesity, and investigate whether their anti-inflammatory properties were affected by modulating the gut microbiota. METHODS AND RESULTS: Twenty-four male rats were assigned randomly to three groups for 8 weeks. Inflammatory status and gut microbiota in HFD-induced obese rats were measured by enzyme linked immunosorbent assay and 16sRNA sequencing technology. The dietary supplementation of Extract of fermented barley with L. plantarum JDM1 (LFBE) reduced HFD-induced obesity and improved insulin sensitivity. LFBE significantly decreased the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines (tumour necrosis factor-α, interleukin [IL]-6, IL-1ß, monocyte chemotactic protein-1), and increased anti-inflammatory cytokines (IL-10) in serum. In addition, LFBE suppressed the activation of nuclear factor-κB (NF-κB) by inhibiting the inhibitor of NF-κB alpha degradation and phosphorylation of JNK/p38 mitogen-activated protein kinases in adipose tissue. Combined with changes in gut microbiota, these results illustrated that LFBE treatment markedly decreased the proportion of the LPS-producing opportunistic pathogens and increased the proportion of Bifidobacterium. CONCLUSIONS: Administration of LFBE has beneficial effects on ameliorating HFD-induced obesity and insulin resistance, lessening HFD-induced gut microbiota dysbiosis and pro-inflammatory cytokines secretion. SIGNIFICANCE AND IMPACT OF THIS STUDY: The results suggest that fermented barley extracts may be a useful functional compound and beneficial to improve inflammatory status and gut microflora.

Effects of sulfated polysaccharides from Laminaria japonica on regularating the gut microbiotan and alleviating intestinal inflammation in obese mice.

Due to their known health-enhancing properties, Laminaria japonica polysaccharides (LJP) may alleviate obesity via unknown mechanisms. This study aimed to investigate beneficial LJP effects and mechanism(s) of action using an animal obesity model (ICR mice fed a high-fat diet). First, LJP were confirmed to consist of sulfated polysaccharides via infrared spectroscopy. Next, LJP administration to mice was found to induce weight loss, reduce liver fat accumulation, and support healthy obesity-related blood serum indicator levels. Notably, LJP treatment significantly reduced TC and LDL levels and significantly increased HDL, LPL, UCP-2, and PPAR-α levels. Furthermore, examinations of tissues of LJP-treated mice revealed significantly reduced intestinal tissue inflammation as compared to corresponding results obtained for untreated obese controls. Additionally, LJP treatment relieved colonic shortening and reduced colonic levels of inflammatory factors TNF-α and IL-6. Further exploration of LJP treatment effects on mouse gut microbiota conducted via fecal 16S rRNA gene sequence-based gut microbiome profiling analysis revealed that LJP treatment increased the Bacteroidetes/Firmicutes ratio and increased gut abundances of probiotics Bacteroides acidifaciens, s_Lactobacillus intestinalis, and s_Lactobacillus murinus. In conclusion, these results collectively suggest that LJP use as a food supplement may alleviate obesity and related gut microbiota dysbiosis and intestinal inflammatory disorders.