Supplementation of a High-Fat Diet with Pentadecylresorcinol Increases the Representation of Akkermansia muciniphila in the Mouse Small and Large Intestines and May Protect against Complications Caused by Imbalanced Nutrition.

Imbalanced nutrition, such as a high-fat/high-carbohydrate diet, is associated with negative effects on human health. The composition and metabolic activity of the human gut microbiota are closely related to the type of diet and have been shown to change significantly in response to changes in food content and food supplement administration. Alkylresorcinols (ARs) are lipophilic molecules that have been found to improve lipid metabolism and glycemic control and decrease systemic inflammation. Furthermore, alkylresorcinol intake is associated with changes in intestinal microbiota metabolic activity. However, the exact mechanism through which alkylresorcinols modulate microbiota activity and host metabolism has not been determined. In this study, alterations in the small intestinal microbiota (SIM) and the large intestinal microbiota (LIM) were investigated in mice fed a high-fat diet with or without pentadecylresorcinol (C15) supplementation. High-throughput sequencing was applied for jejunal and colonic microbiota analysis. The results revealed that C15 supplementation in combination with a high-fat diet could decrease blood glucose levels. High-throughput sequencing analysis indicated that C15 intake significantly increased (p < 0.0001) the abundance of the probiotic bacteria Akkermansia muciniphila and Bifidobacterium pseudolongum in both the small and large intestines and increased the alpha diversity of LIM (p < 0.05), but not SIM. The preliminary results suggested that one of the mechanisms of the protective effects of alkylresorcinol on a high-fat diet is the modulation of the content of SIM and LIM and metabolic activity to increase the probiotic bacteria that alleviate unhealthy metabolic changes in the host.

An orally active carbon monoxide-releasing molecule enhances beneficial gut microbial species to combat obesity in mice.

Carbon monoxide (CO), a gaseous signaling molecule, has shown promise in preventing body weight gain and metabolic dysfunction induced by high fat diet (HFD), but the mechanisms underlying these effects are largely unknown. An essential component in response to HFD is the gut microbiome, which is significantly altered during obesity and represents a target for developing new therapeutic interventions to fight metabolic diseases. Here, we show that CO delivered to the gut by oral administration with a CO-releasing molecule (CORM-401) accumulates in faeces and enriches a variety of microbial species that were perturbed by a HFD regimen. Notably, Akkermansia muciniphila, which exerts salutary metabolic effects in mice and humans, was strongly depleted by HFD but was the most abundant gut species detected after CORM-401 treatment. Analysis of bacterial transcripts revealed a restoration of microbial functional activity, with partial or full recovery of the Krebs cycle, ß-oxidation, respiratory chain and glycolysis. Mice treated with CORM-401 exhibited normalization of several plasma and fecal metabolites that were disrupted by HFD and are dependent on Akkermansia muciniphila's metabolic activity, including indoles and tryptophan derivatives. Finally, CORM-401 treatment led to an improvement in gut morphology as well as reduction of inflammatory markers in colon and cecum and restoration of metabolic profiles in these tissues. Our findings provide therapeutic insights on the efficacy of CO as a potential prebiotic to combat obesity, identifying the gut microbiota as a crucial target for CO-mediated pharmacological activities against metabolic disorders.

The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.

MDG, an Ophiopogon japonicus polysaccharide, inhibits non-alcoholic fatty liver disease by regulating the abundance of Akkermansia muciniphila.

MDG, a polysaccharide derived from Ophiopogon japonicus, displays a protective effect against obesity and non-alcoholic fatty liver disease (NAFLD). However, there is no definitive evidence proving the specific mechanism of MDG against NAFLD. The results showed MDG supplementation ameliorated lipid accumulation, liver steatosis, and chronic inflammation in high-fat diet-induced NAFLD mice. Besides, MDG increased the abundance and diversity of microbial communities in the gut. These effects were mediated by the colonization of fecal microbiota. Further investigation revealed that Akkermansia muciniphila levels correlated negatively with NAFLD development, and lipid metabolism-related signaling might be the key regulator. Our study suggested that MDG treatment could inhibit obesity and the NAFLD process by modulating lipid-related pathways via altering the structure and diversity of gut microbiota. In addition, Akkermansia miniciphila might be a promising candidate in future research into NAFLD.

Polydextrose with and without Bifidobacterium animalis ssp. lactis 420 drives the prevalence of Akkermansia and improves liver health in a multi-compartmental obesogenic mice study.

The past two decades of research have raised gut microbiota composition as a contributing factor to the development of obesity, and higher abundance of certain bacterial species has been linked to the lean phenotype, such as Akkermansia muciniphila. The ability of pre- and probiotics to affect metabolic health could be via microbial community alterations and subsequently changes in metabolite profiles, modulating for example host energy balance via complex signaling pathways. The aim of this mice study was to determine how administration of a prebiotic fiber, polydextrose (PDX) and a probiotic Bifidobacterium animalis ssp. lactis 420 (B420), during high fat diet (HFD; 60 kcal% fat) affects microbiota composition in the gastrointestinal tract and adipose tissue, and metabolite levels in gut and liver. In this study C57Bl/6J mice (N = 200) were split in five treatments and daily gavaged: 1) Normal control (NC); 2) HFD; 3) HFD + PDX; 4) HFD + B420 or 5) HFD + PDX + B420 (HFD+S). At six weeks of treatment intraperitoneal glucose-tolerance test (IPGTT) was performed, and feces were collected at weeks 0, 3, 6 and 9. At end of the intervention, ileum and colon mucosa, adipose tissue and liver samples were collected. The microbiota composition in fecal, ileum, colon and adipose tissue was analyzed using 16S rDNA sequencing, fecal and liver metabolomics were performed by nuclear magnetic resonance (NMR) spectroscopy. It was found that HFD+PDX intervention reduced body weight gain and hepatic fat compared to HFD. Sequencing the mice adipose tissue (MAT) identified Akkermansia and its prevalence was increased in HFD+S group. Furthermore, by the inclusion of PDX, fecal, lleum and colon levels of Akkermansia were increased and liver health was improved as the detoxification capacity and levels of methyl-donors were increased. These new results demonstrate how PDX and B420 can affect the interactions between gut, liver and adipose tissue.

Low molecular weight fucoidan fraction LF2 improves metabolic syndrome via up-regulating PI3K-AKT-mTOR axis and increasing the abundance of Akkermansia muciniphila in the gut microbiota.

Metabolic syndrome (MetS) is a pathological condition of a variety of metabolic abnormalities, which requires more urgent treatment and intervention. Fucoidan has been recommended as a supplement for health enhancement and disease management. Here, we first propose that the beneficial effect of low molecular weight fucoidan fraction LF2 in regulating metabolic syndrome induced by high-fat diet is similar to that of metformin, in terms of molecular mechanism and gut microbiota. The study found that LF2 significantly reduces fasting blood glucose, enhances insulin sensitivity and restores insulin homeostasis and lipid homeostasis. Moreover, LF2 reduced liver oxidative stress and inflammation, and improved hepatocyte steatosis. To decipher the mechanism behind this therapeutic effect, both the molecular mechanisms and gut microbiota were further analyzed. LF2 inhibited the activation of PI3K-Akt-mTOR axis and decreased the expression of SREBP-1c and PPARγ in liver. Interestingly, we found that LF2 and metformin have similar effects on gut microbiota, increasing the proportion of Verrucomicrobia and enriching the abundance of Akkermansia muciniphila, which is beneficial to host health. Collectively, our research clarifies the new application of fucoidan as a functional food for anti-MetS, and provides a new insight for fucoidan to exert systemic therapeutic effects from the perspective of molecular mechanism and gut microbiota.

Akkermansia muciniphila and host interaction within the intestinal tract.

In the modern world, metabolic syndrome is one of the major health problems. Heredity, overeating, and a sedentary lifestyle are believed to be the main predisposing factors for its development. However, recent data indicate that gut microbiota plays a significant role in metabolic profile formation. In 2004, Derrien et al. isolated and characterized the bacterium Akkermansia muciniphila, which lives mainly in the human intestine and has the ability to utilize intestinal mucin. It proved to be a good candidate for the role of a new-generation probiotic due to its ability to improve the laboratory and physical indicators associated with metabolic syndrome and type 2 diabetes in mice and humans. In this review, we describe the basic microbiological characteristics of this bacterium, its main habitats, clinical effects after oral administration, and different ways of influencing the digestive tract. All these data allow us to understand the mechanism of its beneficial effects, which is important for its future introduction into the treatment of the metabolic syndrome.

Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study.

Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equivalent of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metabolism in healthy adults. This study included a 4-week standardization to a low-polyphenol diet, followed by 4 weeks of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 weeks of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addition, there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body composition were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metabolism.

Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment.

The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, we show that microbiota-derived stimulator of interferon genes (STING) agonists induce type I interferon (IFN-I) production by intratumoral monocytes to regulate macrophage polarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation with a high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved the efficacy of immune checkpoint blockade (ICB). We validated our findings in individuals with melanoma treated with ICB and showed that the predicted intratumoral IFN-I and immune compositional differences between responder and non-responder individuals can be transferred by fecal microbiota transplantation. Our study uncovers a mechanistic link between the microbiota and the innate TME that can be harnessed to improve cancer therapies.

Structural Characterization of a Polysaccharide from Gastrodia elata and Its Bioactivity on Gut Microbiota.

A novel homogeneous polysaccharide named GEP-1 was isolated and purified from Gastrodia elata (G. elata) by hot-water extraction, ethanol precipitation, and membrane separator. GEP-1, which has a molecular weight of 20.1 kDa, contains a polysaccharide framework comprised of only glucose. Methylation and NMR analysis showed that GEP-1 contained 1,3,6-linked-α-Glcp, 1,4-linked-α-Glcp, 1,4-linked-ß-Glcp and 1,4,6-linked-α-Glcp. Interestingly, GEP-1 contained citric acid and repeating p-hydroxybenzyl alcohol as one branch. Furthermore, a bioactivity test showed that GEP-1 could significantly promote the growth of Akkermansia muciniphila (A. muciniphila) and Lacticaseibacillus paracasei (L.paracasei) strains. These results implied that GEP-1 might be useful for human by modulating gut microbiota.

Structural characterization of two novel polysaccharides from Gastrodia elata and their effects on Akkermansia muciniphila.

Two homogeneous polysaccharides, GEP-3 and GEP-4, were purified from Gastrodia elata, a precious traditional Chinese medicine. Their structural characteristics were obtained using HPGPC, PMP-HPLC, LC/MS, FT-IR, NMR, and SEM methods. GEP-3 was 1,4-glucan with molecular weight of 20 kDa. Interestingly, GEP-4 comprised of a backbone of →[4)-α-Glcp-(1]10→[4)-α-Glcp-(1→]5[6)-ß-Glcp-(1]11→6)-α-Glcp-(3→ and two branches of ß-Glcp and p-hydroxybenzyl alcohol citrate, with repeating p-hydroxybenzyl alcohol attached to the backbone chain at O-6 position of →4,6)-α-Glcp-(1→ and O-1 position of →3,6)-α-Glcp-(1→. GEP-4 is a novel polysaccharide obtained and characterized for the first time. Bioactivity test indicated that both of them significantly promote the growth of Akkermansia muciniphila (Akk. muciniphila). Furthermore, GEP-3 and GEP-4 promoted the growth of Akk. muciniphila from high-fat diet (HFD) fecal microbiota. These results indicated that GEP-3 and GEP-4 were potential Akk. muciniphila growth promoters.

In-depth analysis of the mechanisms of aloe polysaccharides on mitigating subacute colitis in mice via microbiota informatics.

Aloe polysaccharides (APs) are indigestible bioactive polysaccharides, while can be fermented by colonic microbiota. Although plant polysaccharides can alleviate subacute ulcerative colitis (SUC), the mechanisms APs regulated SUC via colonic microbiota have not been fully explored. Hence, to elucidate the complex interactions between the novel APs, colonic microbiota, SCFAs, and inflammation, the SUC mouse model and in-depth analysis were performed, including multiple bioinformatics analysis and structural equation modeling (SEM). After APs intervention, SCFAs and SCFAs-producing genus, including Akkermansia and Blautia, were increased in colon, and the colonic inflammation and barrier dysfunction were alleviated significantly in SUC mice. Spearman analysis found positive correlations between microbiota and SCFAs. PICRUSt2 and KEGG analysis revealed 6-pyruvoyltetra hydropterin synthase in folate biosynthesis metabolism pathway was activated, while phosphotransferase system was inhibited. SEM results further proved APs was beneficial to gut micro-ecological balance in mice via SCFAs metabolism and anti-inflammatory functions. Together, APs could be exploited to alleviate SUC as dietary therapeutics.

Berberine, a potential prebiotic to indirectly promote Akkermansia growth through stimulating gut mucin secretion.

BACKGROUND: Akkermansia spp. plays important roles in maintenance of host health. Increasing evidence reveals that berberine (BBR) may exert its pharmacological effects via, at least partially, promotion of Akkermansia spp. However, how BBR stimulates Akkermansia remains largely unknown. PURPOSE: In this study, we investigated the mechanism underlying the Akkermansia-promoting effect of BBR. MATERIALS AND METHODS: The effect of BBR on Akkermansia was assessed in BBR-gavaged mice and direct incubation. The influence of BBR on intestinal mucin production was determined by alcian-blue staining and real-time PCR. The feces were analysis by gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) metabolomics. The role of polyamines in BBR-elicited mucin secretion and Akkermansia growth was evaluated by administration of difluoromethylornithine (DFMO) in mice. RESULTS: Gavage of BBR dose-dependently and time-dependently increased the abundance of Akkermansia in mice. However, it did not stimulate Akkermansia growth in direct incubation, suggesting that BBR may promote Akkermansia in a host-dependent way. Oral administration of BBR significantly increased the transcription of mucin-producing genes and mucin secretion in colon. Untargeted metabolomics analysis showed that BBR increased polyamines production in feces which are known to stimulate goblet cell proliferation and differentiation, but treatment with eukaryotic polyamine synthase inhibitor DFMO did not abolish the stimulating effect of BBR on mucin secretion and Akkermansia growth, indicating that the gut bacteria-derived but not the host-derived polyamines may involve in the BBR-promoted Akkermansia growth. CONCLUSIONS: Our results reveal that BBR is a promising prebiotic for Akkermansia, and it promotes Akkermansia growth via stimulating mucin secretion in colon.

Decreased abundance of Akkermansia after adrenocorticotropic hormone therapy in patients with West syndrome.

BACKGROUND: Infants suffer from a severe epileptic encephalopathy known as West syndrome (WS). Treatment with adrenocorticotropic hormone (ACTH) indicates the involvement of the gut-brain axis in WS. Several pieces of evidence show the communication of the gut microbiota (GM) with the brain via the hypothalamic-pituitary-adrenal axis (HPA axis) and blood cytokines. This study aimed at (1) determining the GM diversity in infants having WS and (2) comparing the results of infants having WS with those of the healthy infants and also in the patients with WS before and after the ACTH therapy. RESULTS: In this study, 29 infants with WS and 29 healthy infants aged 3-13 months were recruited. Fecal samples were collected, and DNA was extracted and sequenced on the Illumina MiSeq platform. Kruskal-Wallis rank-sum test was used to analyze the between-group differences in the Chao1 index, Shannon index, and the abundances of GM at different taxonomy levels. R software was used to plot the graphs. The top five dominant GM genera between patients with WS and healthy infants showed no significant differences. However, the relative abundance of genus Akkermansia was observed to be significantly (P = 0.011) higher in the BT group than in the HC group and AT group. After 2 weeks of ACTH therapy, the relative abundance of Akkermansia significantly (P = 0.003) decreased. CONCLUSION: The relative abundance of Akkermansia was observed to be significantly higher in patients with WS than that in healthy infants. However, the relationship between Akkermansia and WS pathogenesis needs to be clarified in further studies.

Lactobacillus acidophilus LA5 improves saturated fat-induced obesity mouse model through the enhanced intestinal Akkermansia muciniphila.

Obesity, a major healthcare problem worldwide, induces metabolic endotoxemia through the gut translocation of lipopolysaccharides (LPS), a major cell wall component of Gram-negative bacteria, causing a chronic inflammatory state. A combination of several probiotics including Lactobacillus acidophilus 5 (LA5), a potent lactic acid-producing bacterium, has previously been shown to attenuate obesity. However, data on the correlation between a single administration of LA5 versus microbiota alteration might be helpful for the probiotic adjustment. LA5 was administered daily together with a high-fat diet (HFD) for 8 weeks in mice. Furthermore, the condition media of LA5 was also tested in a hepatocyte cell-line (HepG2 cells). Accordingly, LA5 attenuated obesity in mice as demonstrated by weight reduction, regional fat accumulation, lipidemia, liver injury (liver weight, lipid compositions, and liver enzyme), gut permeability defect, endotoxemia, and serum cytokines. Unsurprisingly, LA5 improved these parameters and acidified fecal pH leads to the attenuation of fecal dysbiosis. The fecal microbiome analysis in obese mice with or without LA5 indicated; (i) decreased Bacteroidetes (Gram-negative anaerobes that predominate in non-healthy conditions), (ii) reduced total fecal Gram-negative bacterial burdens (the sources of gut LPS), (iii) enhanced Firmicutes (Gram-positive bacteria with potential benefits) and (iv) increased Verrucomycobia, especially Akkermansia muciniphila, a bacterium with the anti-obesity property. With LA5 administration, A. muciniphila in the colon were more than 2,000 folds higher than the regular diet mice as determined by 16S rRNA. Besides, LA5 produced anti-inflammatory molecules with a similar molecular weight to LPS that reduced cytokine production in LPS-activated HepG2 cells. In conclusion, LA5 attenuated obesity through (i) gut dysbiosis attenuation, partly through the promotion of A. muciniphila (probiotics with the difficulty in preparation processes), (ii) reduced endotoxemia, and (iii) possibly decreased liver injury by producing the anti-inflammatory molecules.

Akkermansia muciniphila: A potential novel mechanism of nuciferine to improve hyperlipidemia.

BACKGROUND: Intestinal microbiota is a novel drug target of metabolic diseases, especially for those with poor oral bioavailability. Nuciferine, with poor bioavailability, has an anti-hyperlipidemic effect at low dosages. PURPOSE: In the present study, we aimed to explore the role of intestinal microbiota in the anti-hyperlipidemic function of nuciferine and identify the key bacterial targets that might confer the therapeutic actions. METHODS: The contribution of gut microbes in the anti-hyperlipidemic effect of nuciferine was evaluated by conventional and antibiotic-established pseudo-sterile mice. Whole-metagenome shotgun sequencing was used to characterize the changes in microbial communities by various agents. RESULTS: Nuciferine exhibited potent anti-hyperlipidemic and liver steatosis-alleviating effects at the doses of 7.5-30 mg/kg. The beneficial effects of nuciferine were substantially abolished when combined with antibiotics. Metagenomic analysis showed that nuciferine significantly shifted the microbial structure, and the enrichment of Akkermansia muciniphila was closely related to the therapeutic effect of nuciferine. CONCLUSIONS: Our results revealed that gut microbiota played an essential role in the anti-hyperlipidemic effect of nuciferine, and enrichment of Akkermansia muciniphila represented a key mechanism through which nuciferine exerted its therapeutic effects.

Unravelling the antimicrobial action of antidepressants on gut commensal microbes.

Over the past decade, there has been increasing evidence highlighting the implication of the gut microbiota in a variety of brain disorders such as depression, anxiety, and schizophrenia. Studies have shown that depression affects the stability of gut microbiota, but the impact of antidepressant treatments on microbiota structure and metabolism remains underexplored. In this study, we investigated the in vitro antimicrobial activity of antidepressants from different therapeutic classes against representative strains of human gut microbiota. Six different antidepressants: phenelzine, venlafaxine, desipramine, bupropion, aripiprazole and (S)-citalopram have been tested for their antimicrobial activity against 12 commensal bacterial strains using agar well diffusion, microbroth dilution method, and colony counting. The data revealed an important antimicrobial activity (bacteriostatic or bactericidal) of different antidepressants against the tested strains, with desipramine and aripiprazole being the most inhibitory. Strains affiliating to most dominant phyla of human microbiota such as Akkermansia muciniphila, Bifidobacterium animalis and Bacteroides fragilis were significantly altered, with minimum inhibitory concentrations (MICs) ranged from 75 to 800 µg/mL. A significant reduction in bacterial viability was observed, reaching 5 logs cycle reductions with tested MICs ranged from 400 to 600 µg/mL. Our findings demonstrate that gut microbiota could be altered in response to antidepressant drugs.

Vitamin D Decreases Plasma Trimethylamine-N-oxide Level in Mice by Regulating Gut Microbiota.

As a metabolite generated by gut microbiota, trimethylamine-N-oxide (TMAO) has been proven to promote atherosclerosis and is a novel potential risk factor for cardiovascular disease (CVD). The objective of this study was to examine whether regulating gut microbiota by vitamin D supplementation could reduce the plasma TMAO level in mice. For 16 weeks, C57BL/6J mice were fed a chow (C) or high-choline diet (HC) without or with supplementation of vitamin D3 (CD3 and HCD3) or a high-choline diet with vitamin D3 supplementation and antibiotics (HCD3A). The results indicate that the HC group exhibited higher plasma trimethylamine (TMA) and TMAO levels, lower richness of gut microbiota, and significantly increased Firmicutes and decreased Bacteroidetes as compared with group C. Vitamin D supplementation significantly reduced plasma TMA and TMAO levels in mice fed a high-choline diet. Furthermore, gut microbiota composition was regulated, and the Firmicutes/Bacteroidetes ratio was reduced by vitamin D. Spearman correlation analysis indicated that Bacteroides and Akkermansia were negatively correlated with plasma TMAO in the HC and HCD3 groups. Our study provides a novel avenue for the prevention and treatment of CVD with vitamin D.

Roles of gut microbiota and metabolites in a homogalacturonan-type pectic polysaccharide from Ficus pumila Linn. fruits mediated amelioration of obesity.

In this study, the beneficial effects of a homogalacturonan(HG)-type pectic polysaccharide from Ficus pumila L. fruits (FPLP) in obese mice were investigated. The 17-week FPLP treatment effectively attenuated obesity, as mainly demonstrated by the reductions of body weight, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in high-fat diet (HFD)-induced obese mice. The decreased Firmicutes to Bacteroidetes abundance ratio, enriched Akkermansia, and reduced Blautia abundance suggested that FPLP ameliorated the HFD-induced gut dysbiosis. FPLP also influenced the levels of metabolites altered upon HFD feeding, including increases in myristoleic acid and pentadecanoic acid levels. The correlation studies indicated that FPLP ameliorated HFD-induced rise in TC and LDL-C levels through regulating gut microbial community and their associated metabolites. In conclusion, this study extends our understanding of the relationships among gut microbiota (Akkermansia and Blautia), metabolites (myristoleic acid and pentadecanoic acid), HG-type pectin and its TC- and LDL-C- lowering functions.

Andrographolide Exerts Antihyperglycemic Effect through Strengthening Intestinal Barrier Function and Increasing Microbial Composition of Akkermansia muciniphila.

Accumulating evidence indicates that type 2 diabetes (T2D) is associated with intestinal barrier dysfunction and dysbiosis, implying the potential targets for T2D therapeutics. Andrographolide was reported to have several beneficial effects on diabetes and its associated complications. However, the protective role of andrographolide, as well as its underlying mechanism against T2D, remains elusive. Herein, we reported that andrographolide enhanced intestinal barrier integrity in LPS-induced Caco-2 cells as indicated by the improvement of cell monolayer barrier permeability and upregulation of tight junction protein expression. In addition, andrographolide alleviated LPS-induced oxidative stress by preventing ROS and superoxide anion radical overproduction and reversing glutathione depletion. In line with the in vitro results, andrographolide reduced metabolic endotoxemia and strengthened gut barrier integrity in db/db diabetic mice. We also found that andrographolide appeared to ameliorate glucose intolerance and insulin resistance and attenuated diabetes-associated redox disturbance and inflammation. Furthermore, our results indicated that andrographolide modified gut microbiota composition as indicated by elevated Bacteroidetes/Firmicutes ratio, enriched microbial species of Akkermansia muciniphila, and increased SCFAs level. Taken together, this study demonstrated that andrographolide exerted a glucose-lowering effect through strengthening intestinal barrier function and increasing the microbial species of A. muciniphila, which illuminates a plausible approach to prevent T2D by regulating gut barrier integrity and shaping intestinal microbiota composition.