Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis.

Limosilactobacillus reuteri (L. reuteri) is an efficacious probiotic that could reduce inflammation and prevent metabolic disorders. Here, we innovatively found that Polygonatum kingianum polysaccharides (PKP) promoted proliferation and increased stability of L. reuteri WX-94 (a probiotic strain showing anti-inflammation potentials) in simulated digestive fluids in vitro. PKP was composed of galactose, glucose, mannose, and arabinose. The cell-free supernatant extracted from L. reuteri cultured with PKP increased ABTS•+, DPPH•, and FRAP scavenging capacities compared with the supernatant of the medium without PKP and increased metabolites with health-promoting activities, e.g., 3-phenyllactic acid, indole-3-lactic acid, indole-3-carbinol, and propionic acid. Moreover, PKP enhanced alleviating effects of heat-inactivated L. reuteri on high-fat-high-sucrose-induced liver injury in rats via reducing inflammation and regulating expressions of protein and genes involved in fatty acid metabolism (such as HIF1-α, FAßO, CPT1, and AMPK) and fatty acid profiles in liver. Such benefits correlated with its prominent effects on enriching Lactobacillus and short-chain fatty acids while reducing Dubosiella, Fusicatenilacter, Helicobacter, and Oscillospira. Our work provides novel insights into the probiotic property of PKP and emphasizes the great potential of the inactivated L. reuteri cultured with PKP in contracting unhealthy diet-induced liver dysfunctions and gut dysbacteriosis.

Chronodisruption and Gut Microbiota: Triggering Glycemic Imbalance in People with Type 2 Diabetes.

The desynchronization of physiological and behavioral mechanisms influences the gut microbiota and eating behavior in mammals, as shown in both rodents and humans, leading to the development of pathologies such as Type 2 diabetes (T2D), obesity, and metabolic syndrome. Recent studies propose resynchronization as a key input controlling metabolic cycles and contributing to reducing the risk of suffering some chronic diseases such as diabetes, obesity, or metabolic syndrome. In this analytical review, we present an overview of how desynchronization and its implications for the gut microbiome make people vulnerable to intestinal dysbiosis and consequent chronic diseases. In particular, we explore the eubiosis-dysbiosis phenomenon and, finally, propose some topics aimed at addressing chronotherapy as a key strategy in the prevention of chronic diseases.

Probiotics for Prevention and Treatment of Clostridium difficile Infection.

Probiotics have been claimed as a valuable tool to restore the balance in the intestinal microbiota following a dysbiosis caused by, among other factors, antibiotic therapy. This perturbed environment could favor the overgrowth of Clostridium difficile, and in fact, the occurrence of C. difficile-associated infections (CDI) is increasing in recent years. In spite of the high number of probiotics able to in vitro inhibit the growth and/or toxicity of this pathogen, its application for treatment or prevention of CDI is still scarce since there are not enough well-defined clinical studies supporting efficacy. Only a few strains, such as Lactobacillus rhamnosus GG and Saccharomyces boulardii, have been studied in more extent. The increasing knowledge about the probiotic mechanisms of action against C. difficile, some of them reviewed here, makes promising the application of these live biotherapeutic agents against CDI. Nevertheless, more effort must be paid to standardize the clinical studies conducted to evaluate probiotic products, in combination with antibiotics, in order to select the best candidate for C. difficile infections.

Exercise prevents obesity by reducing gut-derived inflammatory signals to brown adipocytes in mice.

Gut dysbiosis impairs nonshivering thermogenesis (NST) in obesity. The antiobesogenic effects of exercise training might involve the modulation of gut microbiota and its inflammatory signals to the brown adipose tissue (BAT). This study evaluated whether high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) prevent overweight through reduced gut-derived inflammatory signals to BAT in high-fat-fed mice. Sixty male C57BL/6 mice (3 months old) comprised six experimental groups: control (C) diet group, C diet + HIIT (C-HIIT) group, C diet + MICT (C-MICT) group, high-fat (HF) diet group, HF diet + HIIT (HF-HIIT) group, and HF diet + MICT (HF-MICT) group. The protocols lasted for 10 weeks. HIIT and MICT restored body mass, mitigated glucose intolerance, and prevented hyperinsulinemia in HF-trained groups. A chronic HF diet caused dysbiosis, but HIIT and MICT prevented gut dysbiosis and preserved tight junction (TJ) gene expression. HF-HIIT and HF-MICT groups exhibited a similar pattern of goblet cell distribution, agreeing with the decreased plasma lipopolysaccharide concentrations and interscapular BAT (iBAT) Lbp-Cd14-Tlr4 expression. The lowered Nlrp3 and Il1ß in the HF-HITT and HF-MICT groups complied with iBAT thermogenic capacity maintenance. This study shows reliable evidence that HIIT and MICT prevented overweight by restoring the diversity of the gut microbiota phyla and TJ gene expression, thereby reducing inflammatory signals to brown adipocytes with preserved thermogenic capacity. Both exercise modalities prevented overweight, but HIIT rescued Zo-1 and Jam-a gene expression, exerting more potent anti-inflammatory effects than MICT (reduced LPS concentrations), providing a sustained increase in thermogenesis with 78% less distance traveled.

Short-Term Dietary Intervention with Whole Oats Protects from Antibiotic-Induced Dysbiosis.

Antibiotic-induced gut microbiome dysbiosis (AID) is known to be influenced by host dietary composition. However, how and when diet modulates gut dysbiosis remains poorly characterized. Thus, here, we utilize a multi-omics approach to characterize how a diet supplemented with oats, a rich source of microbiota-accessible carbohydrates, or dextrose impacts amoxicillin-induced changes to gut microbiome structure and transcriptional activity. We demonstrate that oat administration during amoxicillin challenge provides greater protection from AID than the always oats or recovery oats diet groups. In particular, the group in which oats were provided at the time of antibiotic exposure induced the greatest protection against AID while the other oat diets saw greater effects after amoxicillin challenge. The oat diets likewise reduced amoxicillin-driven elimination of Firmicutes compared to the dextrose diet. Functionally, gut communities fed dextrose were carbohydrate starved and favored respiratory metabolism and consequent metabolic stress management while oat-fed communities shifted their transcriptomic profile and emphasized antibiotic stress management. The metabolic trends were exemplified when assessing transcriptional activity of the following two common gut commensal bacteria: Akkermansia muciniphila and Bacteroides thetaiotaomicron. These findings demonstrate that while host diet is important in shaping how antibiotics effect the gut microbiome composition and function, diet timing may play an even greater role in dietary intervention-based therapeutics. IMPORTANCE We utilize a multi-omics approach to demonstrate that diets supplemented with oats, a rich source of microbiota-accessible carbohydrates, are able to confer protection against antibiotic-induced dysbiosis (AID). Our findings affirm that not only is host diet important in shaping antibiotics effects on gut microbiome composition and function but also that the timing of these diets may play an even greater role in managing AID. This work provides a nuanced perspective on dietary intervention against AID and may be informative on preventing AID during routine antibiotic treatment.

Pecans and Its Polyphenols Prevent Obesity, Hepatic Steatosis and Diabetes by Reducing Dysbiosis, Inflammation, and Increasing Energy Expenditure in Mice Fed a High-Fat Diet.

Pecans (Carya illinoinensis) are considered a functional food due to the high content of polyunsaturated fatty acids, dietary fiber and polyphenols. To determine the effect of whole pecans (WP) or a pecan polyphenol (PP) extract on the development of metabolic abnormalities in mice fed a high-fat (HF) diet, we fed C57BL/6 mice with a Control diet (7% fat), HF diet (23% fat), HF containing 30% WP or an HF diet supplemented with 3.6 or 6 mg/g of PP for 18 weeks. Supplementation of an HF diet with WP or PP reduced fat mass, serum cholesterol, insulin and HOMA-IR by 44, 40, 74 and 91%, respectively, compared to the HF diet. They also enhanced glucose tolerance by 37%, prevented pancreatic islet hypertrophy, and increased oxygen consumption by 27% compared to the HF diet. These beneficial effects were associated with increased thermogenic activity in brown adipose tissue, mitochondrial activity and AMPK activation in skeletal muscle, reduced hypertrophy and macrophage infiltration of subcutaneous and visceral adipocytes, reduced hepatic lipid content and enhanced metabolic signaling. Moreover, the microbial diversity of mice fed WP or PP was higher than those fed HF, and associated with lower circulating lipopolysaccharides (~83-95%). Additionally, a 4-week intervention study with the HF 6PP diet reduced the metabolic abnormalities of obese mice. The present study demonstrates that WP or a PP extract prevented obesity, liver steatosis and diabetes by reducing dysbiosis, inflammation, and increasing mitochondrial content and energy expenditure. Pecan polyphenols were mainly condensed tannin and ellagic acid derivatives including ellagitannins as determined by LC-MS. Herein we also propose a model for the progression of the HF diet-mediated metabolic disorder based on early and late events, and the possible molecular targets of WP and PP extract in preventive and intervention strategies. The body surface area normalization equation gave a conversion equivalent to a daily human intake dose of 2101-3502 mg phenolics that can be obtained from 110-183 g pecan kernels/day (22-38 whole pecans) or 21.6-36 g defatted pecan flour/day for an average person of 60 kg. This work lays the groundwork for future clinical studies.

Can prebiotics help tackle the childhood obesity epidemic?

Globally, excess weight during childhood and adolescence has become a public health crisis with limited treatment options. Emerging evidence suggesting the involvement of gut microbial dysbiosis in obesity instills hope that targeting the gut microbiota could help prevent or treat obesity. In pre-clinical models and adults, prebiotic consumption has been shown to reduce adiposity partially via restoring symbiosis. However, there is a dearth of clinical research into its potential metabolic benefits in the pediatric population. Here, we provide a succinct overview of the common characteristics of the gut microbiota in childhood obesity and mechanisms of action of prebiotics conferring metabolic benefits. We then summarize available clinical trials in children with overweight or obesity investigating the effects of prebiotics on weight management. This review highlights several controversial aspects in the microbiota-dependent mechanisms by which prebiotics are thought to affect host metabolism that warrant future investigation in order to design efficacious interventions for pediatric obesity.

Adhesive Ergothioneine Hyaluronate Gel Protects against Radiation Gastroenteritis by Alleviating Apoptosis, Inflammation, and Gut Microbiota Dysbiosis.

Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients' life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.

Prebiotic effects of goji berry in protection against inflammatory bowel disease.

The prevalence of inflammatory bowel disease (IBD) is increasing, which is concerning because IBD is a known risk factor for the development of colorectal cancer. Emerging evidence highlights environmental factors, particularly dietary factors and gut microbiota dysbiosis, as pivotal inducers of IBD onset. Goji berry, an ancient tonic food and a nutraceutical supplement, contains a range of phytochemicals such as polysaccharides, carotenoids, and polyphenols. Among these phytochemicals, L. barbarum polysaccharides (LBPs) are the most important functional constituents, which have protective effects against oxidative stress, inflammation, and neurodegeneration. Recently, the beneficial effects of goji berry and associated LBPs consumption were linked to prebiotic effects, which can prevent dysbiosis associated with IBD. This review assessed pertinent literature on the protective effects of goji berry against IBD focusing on the gut microbiota and their metabolites in mediating the observed beneficial effects.

Novel Strategies for Preventing Dysbiosis in the Oral Cavity.

Oral diseases affect over three billion people worldwide, making it one of the most common infections. Recent studies show that one approach to reducing the risk of chronic infections, such as caries, gingivitis, periodontitis, and halitosis, is to control the ecology of the oral microbiome instead of completely removing both the harmful and beneficial microorganisms. This is based on the knowledge that oral diseases are not caused by a single pathogen but rather by a shift in the homeostasis of the entire microbiota, a process known as dysbiosis. Consequently, it is of the utmost importance to implement strategies that are able to prevent and control oral dysbiosis to avoid serious complications, including heart, lung, and other systemic diseases. Conventional treatments include the use of antibiotics, which further disrupt the equilibrium in the oral microbiota, together with the mechanical removal of the decayed cavity area following its formation. Therefore, it is imperative to implement alternative strategies with the potential to overcome the disadvantages of the current therapy, namely, the use of broad-spectrum antibiotics. In this sense, probiotics and postbiotics have received particular attention since they can modulate the oral microbiota and decrease the dysbiotic rate in the oral cavity. However, their mechanisms of action need to be addressed to clarify and drive their possible applications as preventive strategies. In this sense, this review provides an overview of the potential of probiotics and postbiotics, focusing on their antimicrobial and antibiofilm activities as well as their ability to modulate the inflammatory response. Finally, it also showcases the main advantages and disadvantages of orodispersible films-a promising delivery mechanism for both probiotics and postbiotics to target oral dysbiosis.

Black corn (Zea mays L.) flour has the potential to improve the gut microbiota composition and goblet cell proliferation in mice fed a high-fat diet.

High-fat diets are associated with intestinal dysbiosis and leaky gut leading to intestinal inflammation. Bioactive components, including phenolic compounds, isolated or in their original food matrix, have alleviated intestinal impairments promoted by a high-fat diet. Black corn (Zea mays L.) is a colored corn in which anthocyanins are the most abundant bioactive compound. Thus, we hypothesized that black corn flour may have preventive effects on poor intestinal health in mice fed a high-fat diet. To study this, 30 C57BL/6 mice were randomly divided into 3 experimental groups receiving the following diets for 8 weeks: normal control (fed a normal diet); high-fat (fed a high-fat diet: 60% of calories from fat); high-fat corn (fed a high-fat diet added with 20% of black corn whole flour). The cecal microbiota analyzed by 16S ribosomal RNA sequencing showed that black corn flour intake increased the relative abundance of Ruminococcus, Roseburia, and Prevotellaceae_UCG-001, and decreased Bacteroides and Faecalibaculum. No difference was observed in the cecal short-chain fatty acids and fecal pH among the experimental groups (P > .05). Further, the consumption of black corn flour improved cecal morphology by increasing the number of goblet cells but with no difference in the crypt depth and width. These findings suggest that black corn flour as a source of anthocyanins could have preventive effects on gut dysbiosis resulting from a high-fat diet. SCFA, short chain fatty acids.

Gut microbiota: An emerging therapeutic approach of herbal medicine for prevention of colorectal cancer.

The gut dysbiosis has emerged as a prominent player in the pathogenesis and development of colorectal cancer (CRC), which in turn intensifies dysregulated gut microbiota composition and inflammation. Since most drugs are given orally, this dysbiosis directly and indirectly impinges the absorption and metabolism of drugs in the gastrointestinal tract, and subsequently affects the clinical outcome of patients with CRC. Herbal medicine, including the natural bioactive products, have been used traditionally for centuries and can be considered as novel medicinal sources for anticancer drug discovery. Due to their various structures and pharmacological effects, natural products have been found to improve microbiota composition, repair intestinal barrier and reduce inflammation in human and animal models of CRC. This review summarizes the chemo-preventive effects of extracts and/or compounds derived from natural herbs as the promising antineoplastic agents against CRC, and will provide innovative strategies to counteract dysregulated microbiota and improve the lives of CRC patients.

Regulatory Effect of Isomaltodextrin on a High-Fat Diet Mouse Model with LPS-Induced Low-Grade Chronic Inflammation.

This study aimed to identify the effects of isomaltodextrin (IMD) on sustaining the gut integrity and microbiota composition in a high-fat diet (HFD) with a lipopolysaccharide (LPS)-induced low-grade inflammation mouse model. The homeostasis of the immune response is important to reduce the risk of developing metabolic syndromes. The results of this study showed that pre-treatment of IMD at 5% (w/v) suppressed the concentration of endotoxin and pro-inflammatory mediators TNF-α, MCP-1, and IL-6 while increasing the adiponectin level in the plasma. Subsequently, IMD supplementation maintained the structural integrity and intestinal permeability by upregulating the tight junction protein expressions, leading to reducing D-mannitol concentration in the blood. In addition, dysbiosis was observed in mice induced by HFD plus LPS, suggesting that unhealthy dietary factors elicit metabolic endotoxemia and associated dysbiosis to impair the barrier function. However, IMD supplementation was shown to restore the microbial diversity, promote the growth of Bacteroides-Prevotella, and upregulate the related d-glucarate and d-galactarate degradation pathways, together demonstrating the benefits of IMD as a prebiotic able to promote energy homeostasis. Our results also showed that the blood lipid profile and glucose level in the low-grade inflammation mouse model were modulated by IMD. Moreover, IMD supplementation effectively prevented the metabolic disorder and modulated immune responses in inflamed white adipose tissues by inhibiting the macrophage infiltration and restoring the adiponectin, PPAR-γ, and IRS-1 expression. These findings provide strong evidence for IMD to be a potential prebiotic that acts to sustain a healthy gut microbiota composition and barrier function. By protecting against an unhealthy diet-impaired metabolic balance and maintaining immune homeostasis, IMD may affect the development of metabolic disorders.

Glucosylated nanoparticles for the oral delivery of antibiotics to the proximal small intestine protect mice from gut dysbiosis.

Orally delivered antibiotics can reach the caecum and colon, and induce gut dysbiosis. Here we show that the encapsulation of antibiotics in orally administered positively charged polymeric nanoparticles with a glucosylated surface enhances absorption by the proximal small intestine through specific interactions of glucose and the abundantly expressed sodium-dependent glucose transporter 1. This improves bioavailability of the antibiotics, and limits their exposure to flora in the large intestine and their accumulation in caecal and faecal contents. Compared with the standard administration of the same antibiotics, the oral administration of nanoparticle-encapsulated ampicillin, chloramphenicol or vancomycin in mice with bacterial infections in the lungs effectively eliminated the infections, decreased adverse effects on the intestinal microbiota by protecting the animals from dysbiosis-associated metabolic syndromes and from opportunistic pathogen infections, and reduced the accumulation of known antibiotic-resistance genes in commensal bacteria. Glucosylated nanocarriers may be suitable for the oral delivery of other drugs causing gut dysbiosis.

Omega-3 Fatty Acids and Their Interaction with the Gut Microbiome in the Prevention and Amelioration of Type-2 Diabetes.

Type-2 diabetes mellitus (T2DM) is often linked with hyperglycemia, disturbed lipid profiles, inflammation, and gut dysbiosis. Omega-3 fatty acid supplementation has a vital role in the management of T2DM. As a result, a better understanding of the potential role of omega-3 fatty acids in the development and progression of T2DM by influencing the intestinal microflora will help to improve the therapeutic intervention for T2DM and related complications. Focusing on the molecular mechanisms and signaling pathways induced by omega-3 fatty acids, this paper attempts to comprehensively review and discuss the putative associations between omega-3 fatty acids, gut dysbiosis, and the pathophysiology of T2DM and its related comorbidities. In addition, we contemplate the importance of gut microbiota in T2DM prevention and treatment and ponder the role of omega-3 fatty acids in T2DM by positively modulating gut microbiota, which may lead to discovery of novel targets and therapeutic strategies thereby paving way for further comprehensive, mechanistic, and clinical studies.

Bifidobacterium longum CCFM752 prevented hypertension and aortic lesion, improved antioxidative ability, and regulated the gut microbiome in spontaneously hypertensive rats.

Oxidative stress and gut dysbiosis are important risk factors for hypertension. In this study, the preventive effect of Bifidobacterium longum CCFM752 (CCFM752) on hypertension was evaluated. 5-week-old spontaneously hypertensive rats (SHR) were treated with vehicle or CCFM752 (1.0 × 109 CFU day-1) for 12 weeks. The increase in systolic blood pressure and diastolic blood pressure was significantly prevented by CCFM752 treatment. Simultaneously, CCFM752 prevented aortic fibrosis and hypertrophy and increased aortic endothelial nitric oxide synthase (eNOS) activity. CCFM752 presented an antioxidative effect by inhibiting aortic NADPH oxidase activation and increasing aortic and serum catalase activity, and reducing aortic reactive oxygen species (ROS). The gut dysbiosis of SHR, including the increased Firmicutes/Bacteroidetes ratio, decreased Actinobacteria as well as reduced α-diversity, were restored by CCFM752. CCFM752 also increased the prevalence of Bifidobacterium and Lactobacillus, while decreasing Turicibacter at the genus level. Furthermore, serum metabolomic analysis revealed that CCFM752 up-regulated serum proline and pyridoxamine 5'-phosphate, both of which were negatively correlated with blood pressure. In conclusion, the positive impact of CCFM752 on the gut microbiota may contribute to the antioxidative effect as well as its preventive effect on hypertension.

An engineered live biotherapeutic for the prevention of antibiotic-induced dysbiosis.

Antibiotic-induced alterations in the gut microbiota are implicated in many metabolic and inflammatory diseases, increase the risk of secondary infections and contribute to the emergence of antimicrobial resistance. Here we report the design and in vivo performance of an engineered strain of Lactococcus lactis that altruistically degrades the widely used broad-spectrum antibiotics ß-lactams (which disrupt commensal bacteria in the gut) through the secretion and extracellular assembly of a heterodimeric ß-lactamase. The engineered ß-lactamase-expression system does not confer ß-lactam resistance to the producer cell, and is encoded via a genetically unlinked two-gene biosynthesis strategy that is not susceptible to dissemination by horizontal gene transfer. In a mouse model of parenteral ampicillin treatment, oral supplementation with the engineered live biotherapeutic minimized gut dysbiosis without affecting the ampicillin concentration in serum, precluded the enrichment of antimicrobial resistance genes in the gut microbiome and prevented the loss of colonization resistance against Clostridioides difficile. Engineered live biotherapeutics that safely degrade antibiotics in the gut may represent a suitable strategy for the prevention of dysbiosis and its associated pathologies.

The potential of probiotics in the amelioration of hyperuricemia.

Hyperuricemia is a common disease caused by metabolic disorders or the excessive intake of high-purine foods. Persistent hyperuricemia in extreme cases induces gout, and asymptomatic hyperuricemia is probably linked to other metabolic diseases, such as hypertension. The typical damage caused by asymptomatic hyperuricemia includes inflammation, oxidative stress and gut dysbiosis. Probiotics have broad potential applications as food additives, not as drug therapies, in the amelioration of hyperuricemia. In this review, we describe novel methods for potential hyperuricemia amelioration with probiotics. The pathways through which probiotics may ameliorate hyperuricemia are discussed, including the decrease in uric acid production through purine assimilation and XOD (xanthine oxidase) inhibition as well as enhanced excretion of uric acid production by promoting ABCG2 (ATP binding cassette subfamily G member 2) activity, respectively. Three possible probiotic-related therapeutic pathways for alleviating the syndrome of hyperuricemia are also summarized. The first mechanism is to alleviate the oxidation and inflammation induced by hyperuricemia through the inhibition of NLRP3 inflammasome, the second is to restore damaged intestinal epithelium barriers and prevent gut microbiota dysbiosis, and the third is to enhance the innate immune system by increasing the secretion of immunoglobulin A (sIgA) to resist the stimulus by hyperuricemia. We propose that future research should focus on superior strain resource isolation and insight into the cause-effect mechanisms of probiotics for hyperuricemia amelioration. The safety and effects of the application of probiotics in clinical use also need verification.

Inhibition of gut microbial ß-glucuronidase effectively prevents carcinogen-induced microbial dysbiosis and intestinal tumorigenesis.

The bidirectional interaction between carcinogens and gut microbiota that contributes to colorectal cancer is complicated. Reactivation of carcinogen metabolites by microbial ß-glucuronidase (ßG) in the gut potentially plays an important role in colorectal carcinogenesis. We assessed the chemoprotective effects and associated changes in gut microbiota induced by pre-administration of bacterial-specific ßG inhibitor TCH-3511 in carcinogen azoxymethane (AOM)-treated APCMin/+ mice. AOM induced intestinal ßG activity, which was reflected in increases in the incidence, formation, and number of tumors in the intestine. Notably, inhibition of gut microbial ßG by TCH-3511 significantly reduced AOM-induced intestinal ßG activity, decreased the number of polyps in both the small and large intestine to a frequency that was similar in mice without AOM exposure. AOM also led to lower diversity and altered composition in the gut microbiota with a significant increase in mucin-degrading Akkermansia genus. Conversely, mice treated with TCH-3511 and AOM exhibited a more similar gut microbiota structure as mice without AOM administration. Importantly, TCH-3511 treatment significant decreased Akkermansia genus and produced a concomitant increase in short-chain fatty acid butyrate-producing gut commensal microbes Lachnoospiraceae NK4A136 group genus in AOM-treated mice. Taken together, our results reveal a key role of gut microbial ßG in promoting AOM-induced gut microbial dysbiosis and intestinal tumorigenesis, indicating the chemoprotective benefit of gut microbial ßG inhibition against carcinogens via maintaining the gut microbiota balance and preventing cancer-associated gut microbial dysbiosis. Thus, the bacterial-specific ßG inhibitor TCH-3511 is a potential chemoprevention agent for colorectal cancer.

Food-derived cyanidin-3-O-glucoside reverses microplastic toxicity via promoting discharge and modulating the gut microbiota in mice.

Microplastics (MPs) ingested and accumulated by organisms would ultimately pose a threat to humans via the food chain. A balanced gut microbiota contributes to many health benefits, which is readily influenced by environmental chemicals such as MPs. Cyanidin-3-O-glucoside (C3G), a bioactive compound of the anthocyanin family, possesses a variety of functional effects including anti-oxidant and anti-inflammatory, as well as gut microbiota modulation. C3G has been demonstrated to prevent polystyrene (PS) induced toxicities in Caco-2 cells and Caenorhabditis elegans (C. elegans) via activating autophagy and promoting discharge. In the present study, we aimed to explore the alleviation effect of C3G on PS induced toxicities in C57BL/6 mice. Our results showed that the supplementation of C3G effectively reduced the tissue accumulation and promoted the fecal PS discharge, leading to alleviation of the PS-caused oxidative stress and inflammatory response. Meanwhile, C3G modulated PS-associated gut microbiome perturbations and regulated functional bacteria in inflammation such as Desulfovibrio, Helicobacter, Oscillospiraceae and Lachnoclostridium. Also, C3G administration initiated alterations in functional pathways in response to xenobiotic PS, and reduced bacterial functional genes related to inflammation and human diseases. These findings may offer evidence for the protective role of C3G in the intervention of PS-induced toxicity and gut dysbiosis.