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INTRODUCTION: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved. METHODS: This study represents the in augural analysis of the placebos influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835. RESULTS AND DISCUSSION: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among healthy gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.

Obesity is a major health problem in dogs and is strongly associated with an increased risk of chronic inflammatory and metabolic diseases. The microaerophilic human gut bacterium Akkermansia muciniphila has been proposed as a potential preventive and therapeutic agent against obesity in both humans and mice; however, the protective effects of human-derived A. muciniphila against canine obesity remain unstudied. We previously demonstrated that the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the faeces of a healthy Korean exerts similar protective effects as the live bacterium in mice with high-fat-diet (HFD)-induced obesity. Here, we evaluated the effects of AMDK19-HK on body weight, body fat mass, haematological and biochemical parameters, and faecal microbiota composition in beagles fed an HFD for 12 weeks. AMDK19-HK supplementation effectively suppressed body weight increase, body fat deposition and serum triglyceride increase in the canine model; however, no significant changes in the overall haematological and biochemical parameters were observed, reflecting the direct anti-obesity effect of AMDK19-HK. Additionally, 16S rRNA gene sequencing revealed that AMDK19-HK supplementation induced significant changes in the faecal bacterial community, with an increased abundance of Firmicutes and a decreased abundance of Bacteroidota. These results suggest that AMDK19-HK can be used as a dietary supplement to counteract diet-induced overweight in dogs. [ABSTRACT FROM AUTHOR]

Although Akkermansia muciniphila (Am) plays a beneficial role as a probiotic in the treatment of metabolic syndrome, the mechanisms remain elusive. We tested the hypothesis that Am extracellular vesicles (AmEVs) protect against hypertension through modulation of gene expression in the kidneys of spontaneously hypertensive rats (SHRs). Extracellular vesicles purified from anaerobically cultured Am (1.0 × 108 or 1.0 × 109 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and SHRs weekly for 4 weeks. Renal cortical tissues isolated from both rat strains were analyzed by trichrome stain and RT-qPCR. AmEVs protect against the development of hypertension in SHRs without a serious adverse reaction. AmEVs increased the expression of vasocontracting Agt and At1ar as well as vasodilating At2r, Mas1 and Nos2 in the kidneys of both strains. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Intestinal barriers play a crucial role in human physiology, both in homeostatic and pathological conditions. Disruption of the intestinal barrier is a significant factor in the pathogenesis of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. The profound influence of the gut microbiota on intestinal diseases has sparked considerable interest in manipulating it through dietary interventions, probiotics, and fecal microbiota transplantation as potential approaches to enhance the integrity of the intestinal barrier. Numerous studies have underscored the protective effects of specific microbiota and their associated metabolites. In recent years, an increasing body of research has demonstrated that Akkermansia muciniphila (A. muciniphila, Am) plays a beneficial role in various diseases, including diabetes, obesity, aging, cancer, and metabolic syndrome. It is gaining popularity as a regulator that influences the intestinal flora and intestinal barrier and is recognized as a 'new generation of probiotics'. Consequently, it may represent a potential target and promising therapy option for intestinal diseases. This article systematically summarizes the role of Am in the gut. Specifically, we carefully discuss key scientific issues that need resolution in the future regarding beneficial bacteria represented by Am, which may provide insights for the application of drugs targeting Am in clinical treatment. [ABSTRACT FROM AUTHOR]

Due to its physiological benefits from in vitro and in vivo points of view, Akkermansia muciniphila, a common colonizer in the human gut mucous layer, has consistently been identified as an option for the next-generation probiotic. A. muciniphila is a significant bacterium that promotes host physiology. However, it also has a great deal of potential to become a probiotic due to its physiological advantages in a variety of therapeutic circumstances. Therefore, it can be established that the abundance of A. muciniphila in the gut environment, which is controlled by many genetic and dietary variables, is related to the biological behaviors of the intestinal microbiota and gut dysbiosis/eubiosis circumstances. Before A. muciniphila is widely utilized as a next-generation probiotic, regulatory obstacles, the necessity for significant clinical trials, and the sustainability of manufacturing must be eliminated. In this review, the outcomes of recent experimental and clinical reports are comprehensively reviewed, and common colonization patterns, main factors involved in the colonization of A. muciniphila in the gut milieu, their functional mechanisms in establishing homeostasis in the metabolic and energy pathways, the promising delivery role of microencapsulation, potential genetic engineering strategies, and eventually safety issues of A. muciniphila have been discussed. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is initially sensitive to androgen deprivation therapy (ADT) but ultimately develops resistance and progresses to castration-resistant prostate cancer (CRPC) with a poor prognosis. This study indicated that some PCa patients and mice were more sensitive to ADT and entered CRPC later, which was related to the gut microbiota, especially the enrichment of Akkermansia muciniphila (AKK). Untargeted metabolomics analysis found that serum inosine level was upregulated in the treatment-sensitive group and significantly correlated with AKK. Furthermore, we revealed that intestinal permeability and serum lipopolysaccharide (LPS) levels increased in treatment-resistant mice. LPS stimulated the upregulation of p-NF-κB p65 and AR in tumors. Supplementing AKK metabolite inosine could alleviate intestinal barrier damage and reduce serum LPS level, ultimately inhibiting castration resistance via the LPS/NF-κB/AR axis. Finally, we constructed a predictive model for CRPC combining gut microbiota and clinical information (AUC = 0.729). This study revealed the potential mechanism of gut microbiota on CRPC and provided potential therapeutic targets and prognostic indicators. [ABSTRACT FROM AUTHOR]

Akkermansia muciniphila (A. muciniphila) and its derivatives, including extracellular vesicles (EVs) and outer membrane proteins, are recognized for enhancing intestinal balance and metabolic health. However, the mechanisms of Akkermansia muciniphila's action and its effects on the microbiome are not well understood. In this study, we examined the influence of A. muciniphila and its derivatives on gastrointestinal (GI) and metabolic disorders through a meta-analysis of studies conducted on mouse models. A total of 39 eligible studies were identified through targeted searches on PubMed, Web of Science, Science Direct, and Embase until May 2024. A. muciniphila (alive or heat-killed) and its derivatives positively affected systemic and gut inflammation, liver enzyme level, glycemic response, and lipid profiles. The intervention increased the expression of tight-junction proteins in the gut, improving gut permeability in mouse models of GI and metabolic disorders. Regarding body weight, A. muciniphila and its derivatives prevented weight loss in animals with GI disorders while reducing body weight in mice with metabolic disorders. Sub-group analysis indicated that live bacteria had a more substantial effect on most analyzed biomarkers. Gut microbiome analysis using live A. muciniphila identified a co-occurrence cluster, including Desulfovibrio, Family XIII AD3011 group, and Candidatus Saccharimonas. Thus, enhancing the intestinal abundance of A. muciniphila and its gut microbial clusters may provide more robust health benefits for cardiometabolic, and age-related diseases compared with A. muciniphila alone. The mechanistic insight elucidated here will pave the way for further exploration and potential translational applications in human health. [ABSTRACT FROM AUTHOR]

Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota‐derived 3‐hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6‐mediated radiation damage. Irradiated cell‐fecal microbiota co‐culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43‐mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut‐immune axis in radiation pathophysiology, with potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Introduction: Ulcerative colitis is an inflammatory disorder characterized by chronic inflammation in the gastrointestinal tract, mainly in the colon and rectum. Although the precise etiology of ulcerative colitis remains unclear, recent research has underscored the significant role of the microbiome in its development and progression. Methods: The aim of this study was to establish a relationship between the levels of specific gut bacterial species and disease relapse in ulcerative colitis. For this study, we recruited 105 ulcerative colitis patients in remission and collected clinical data, blood, and stool samples. Akkermansia muciniphila and Parabacteroides distasonis levels were quantified in the stool samples of ulcerative colitis patients. Binary logistic regression was applied to collected data to predict disease remission. Results: The median time in remission in this cohort was four years. A predictive model incorporating demographic information, clinical data, and the levels of Akkermansia muciniphila and Parabacteroides distasonis was developed to understand remission patterns. Discussion: Our findings revealed a negative correlation between the levels of these two microorganisms and the duration of remission. These findings highlight the importance of the gut microbiota in ulcerative colitis for disease prognosis and for personalized treatments based on microbiome interventions. [ABSTRACT FROM AUTHOR]

The activation of the vitamin D receptor (VDR) in the ileum has been shown to regulate Paneth cell-specific defensins, a large family of antimicrobial peptides; hence, this may serve as a potential mechanism to maintain intestinal homeostasis. Previously, we have demonstrated that a combination of vitamin D3 (VD) and fructooligosaccharides (FOSs) upregulates colonic Vdr in mice. Here, we aim to examine the effect of VD, alone or in combination with FOSs, on intestinal barrier integrity and the secretion of antimicrobial peptides, as well as the gut microbial community. Male and female C57BL/6J mice at 6 weeks old were randomized into three groups to receive the following dietary regimens (n = 10/sex/group) for 8 weeks: (1) standard AIN-93G control diet (CTR), (2) CTR + 5000 IU vitamin D3 (VD), and (3) VD + 5% fructooligosaccharides (VF). VD and VF differentially regulated the mRNA expressions of tight junction proteins in the colon and ileum. VF suppressed the upregulation of colonic ZO-1 and occludin, which was induced by VD supplementation alone. In the ileum, occludin but not ZO-1 was upregulated 20-fold in the VF-treated mice. While VD did not alter the mRNA expressions of Vdr and defensins in the ileum, these targets were downregulated by VF. Microbial analysis further reveals a shift of microbial beta diversity and a reduction in Romboutsia ilealis, a pathobiont, in VF-treated mice. Though the implications of these phenotypical and microbial changes remain to be determined, the administration of FOSs in the presence of VD may serve as an effective dietary intervention for maintaining intestinal homeostasis. [ABSTRACT FROM AUTHOR]

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression. [ABSTRACT FROM AUTHOR]

The qualified presumption of safety (QPS) process was developed to provide a safety assessment approach for microorganisms intended for use in food or feed chains. In the period covered by this statement, no new information was found that would change the status of previously recommended QPS TUs. The TUs in the QPS list were updated based on a verification, against their respective authoritative databases, of the correctness of the names and completeness of synonyms. A new procedure has been established to ensure the TUs are kept up to date in relation to recent taxonomical insights. Of 81 microorganisms notified to EFSA between October 2023 and March 2024 (45 as feed additives, 25 as food enzymes or additives, 11 as novel foods), 75 were not evaluated because: 15 were filamentous fungi, 1 was Enterococcus faecium, 10 were Escherichia coli, 1 was a Streptomyces (all excluded from the QPS evaluation) and 46 were TUs that already have a QPS status. Two of the other eight notifications were already evaluated for a possible QPS status in the previous Panel Statement: Heyndrickxia faecalis (previously Weizmannia faecalis) and Serratia marcescens. One was notified at genus level so could not be assessed for QPS status. The other five notifications belonging to five TUs were assessed for possible QPS status. Akkermansia muciniphila and Actinomadura roseirufa were still not recommended for QPS status due to safety concerns. Rhizobium radiobacter can be recommended for QPS status with the qualification for production purposes. Microbacterium arborescens and Burkholderia stagnalis cannot be included in the QPS list due to a lack of body of knowledge for its use in the food and feed chain and for B. stagnalis also due to safety concerns. A. roseirufa and B. stagnalis have been excluded from further QPS assessment. [ABSTRACT FROM AUTHOR]

Background: Tsumura-Suzuki non-obese (TSNO) mice exhibit a severe form of metabolic dysfunction-associated steatohepatitis (MASH) with advanced liver fibrosis upon feeding a high-fat/cholesterol/cholate-based (iHFC) diet. Another ddY strain, Tsumura-Suzuki diabetes obese (TSOD) mice, are impaired in the progression of iHFC diet-induced MASH. Aim: To elucidate the underlying mechanisms contributing to the differences in MASH progression between TSNO and TSOD mice. Methods: We analyzed differences in the immune system, gut microbiota, and bile acid metabolism in TSNO and TSOD mice fed with a normal diet (ND) or an iHFC diet. Results: TSOD mice had more anti-inflammatory macrophages in the liver than TSNO mice under ND feeding, and were impaired in the iHFC diet-induced accumulation of fibrosis-associated macrophages and formation of histological hepatic crown-like structures in the liver. The gut microbiota of TSOD mice also exhibited a distinct community composition with lower diversity and higher abundance of Akkermansia muciniphila compared with that in TSNO mice. Finally, TSOD mice had lower levels of bile acids linked to intestinal barrier disruption under iHFC feeding. Conclusions: The dynamics of liver macrophage subsets, and the compositions of the gut microbiota and bile acids at steady state and post-onset of MASH, had major impacts on MASH development. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1(GLP-1) is an incretin hormone secreted primarily from the intestinal L-cells in response to meals. GLP-1 is a key regulator of energy metabolism and food intake. It has been proven that P9 protein from A. muciniphila could increase GLP-1 release and improve glucose homeostasis in HFD-induced mice. To obtain an engineered Lactococcus lactis which produced P9 protein, mature polypeptide chain of P9 was codon-optimized, fused with N-terminal signal peptide Usp45, and expressed in L. lactis NZ9000. Heterologous secretion of P9 by recombinant L. lactis NZP9 were successfully detected by SDS-PAGE and western blotting. Notably, the supernatant of L. lactis NZP9 stimulated GLP-1 production of NCI-H716 cells. The relative expression level of GLP-1 biosynthesis gene GCG and PCSK1 were upregulated by 1.63 and 1.53 folds, respectively. To our knowledge, this is the first report on the secretory expression of carboxyl-terminal processing protease P9 from A. muciniphila in L. lactis. Our results suggest that genetically engineered L. lactis which expressed P9 may have therapeutic potential for the treatment of diabetes, obesity and other metabolic disorders. [ABSTRACT FROM AUTHOR]

Disruption of the gut microbiota causes metabolic dysfunction, and intervention in the gut microbiota has the potential to improve host glucose metabolism. Akkermanisa muciniphila is an intestinal bacterium involved in anti-obesity and insulin resistance. Developing interventions to increase A. muciniphla would be useful for new treatment strategies. In this study, we screened herbal drug extracts that promoted the growth of A. muciniphila. Among the 123 herbal drugs, five herbal drug extracts significantly increased A. muciniphila DNA levels compared with that in controls. In particular, Dioscoreae rhizoma extract increased the growth of A. muciniphila in the intestines of mice fed a high-fat diet and improved obesity. It significantly reduced body weight gain, improved glucose tolerance even when the administration was initiated after the induction of dietary obesity. These results suggest that herbal drug extracts, such as Dioscoreae rhizome, that increase A. muciniphila could be a new therapeutic strategy for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Abstract Although Akkermansia muciniphila (Am) plays a beneficial role as a probiotic in the treatment of metabolic syndrome, the mechanisms remain elusive. We tested the hypothesis that Am extracellular vesicles (AmEVs) protect against hypertension through modulation of gene expression in the kidneys of spontaneously hypertensive rats (SHRs). Extracellular vesicles purified from anaerobically cultured Am (1.0 × 108 or 1.0 × 109 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and SHRs weekly for 4 weeks. Renal cortical tissues isolated from both rat strains were analyzed by trichrome stain and RT-qPCR. AmEVs protect against the development of hypertension in SHRs without a serious adverse reaction. AmEVs increased the expression of vasocontracting Agt and At1ar as well as vasodilating At2r, Mas1 and Nos2 in the kidneys of both strains. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension.

Abstract Intestinal barriers play a crucial role in human physiology, both in homeostatic and pathological conditions. Disruption of the intestinal barrier is a significant factor in the pathogenesis of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. The profound influence of the gut microbiota on intestinal diseases has sparked considerable interest in manipulating it through dietary interventions, probiotics, and fecal microbiota transplantation as potential approaches to enhance the integrity of the intestinal barrier. Numerous studies have underscored the protective effects of specific microbiota and their associated metabolites. In recent years, an increasing body of research has demonstrated that Akkermansia muciniphila (A. muciniphila, Am) plays a beneficial role in various diseases, including diabetes, obesity, aging, cancer, and metabolic syndrome. It is gaining popularity as a regulator that influences the intestinal flora and intestinal barrier and is recognized as a ‘new generation of probiotics’. Consequently, it may represent a potential target and promising therapy option for intestinal diseases. This article systematically summarizes the role of Am in the gut. Specifically, we carefully discuss key scientific issues that need resolution in the future regarding beneficial bacteria represented by Am, which may provide insights for the application of drugs targeting Am in clinical treatment.

Background: Trimethylamine-N-Oxide (TMAO) is believed to be linked to increased likelihood of cardiovascular disease. While probiotics have shown limited effectiveness in reducing TMAO levels, the potential of postbiotics remains underexplored. This study aimed to evaluate the impact of Akkermansia muciniphila (A. muciniphila) postbiotic administration on choline-induced TMAO production in mice by modifying the gut microbiota. Methods: Female C57BL/6J mice were divided into six groups, including a control group, high-choline diet group, live A. muciniphila probiotic group, pasteurized A. muciniphila postbiotic group, sodium butyrate group, and sodium propionate group. Various measurements and analyses were conducted, including TMAO and TMA levels in serum, urine, and cecal contents, as well as the expression of FXR and FMO3 in liver tissues. Additionally, metabolic parameters, body weight, serum lipid profile, hepatic protein expression (FMO3, FXR, CutC, and CutD), and gut microbiota composition were assessed. Results: Administration of A. muciniphila postbiotic significantly reduced choline-induced plasma TMAO levels in mice. Furthermore, improvements in serum lipid profiles and liver enzyme levels suggested potential enhancements in lipid metabolism and liver function. The study also observed modulation of specific proteins related to TMAO production and metabolism, including CutC and CutD. Conclusion: The findings highlight the potential of A. muciniphila postbiotics as a dietary strategy for mitigating cardiovascular disease risk by modulating the gut-TMAO axis. Postbiotics, particularly A. muciniphila, offer advantages over probiotics and warrant further investigation for their therapeutic applications in gastrointestinal and metabolic disorders. [ABSTRACT FROM AUTHOR]

The use of next-generation probiotics (NGP) in pigs for combating diseases has been subject to limited research. Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut health. In the first screening experiment, we found that the abundance of A. muciniphila peaked at 14 d old but decreased at weaning (21 d old; P

Abstract The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility.

Abstract Background Trimethylamine-N-Oxide (TMAO) is believed to be linked to increased likelihood of cardiovascular disease. While probiotics have shown limited effectiveness in reducing TMAO levels, the potential of postbiotics remains underexplored. This study aimed to evaluate the impact of Akkermansia muciniphila (A. muciniphila) postbiotic administration on choline-induced TMAO production in mice by modifying the gut microbiota. Methods Female C57BL/6J mice were divided into six groups, including a control group, high-choline diet group, live A. muciniphila probiotic group, pasteurized A. muciniphila postbiotic group, sodium butyrate group, and sodium propionate group. Various measurements and analyses were conducted, including TMAO and TMA levels in serum, urine, and cecal contents, as well as the expression of FXR and FMO3 in liver tissues. Additionally, metabolic parameters, body weight, serum lipid profile, hepatic protein expression (FMO3, FXR, CutC, and CutD), and gut microbiota composition were assessed. Results Administration of A. muciniphila postbiotic significantly reduced choline-induced plasma TMAO levels in mice. Furthermore, improvements in serum lipid profiles and liver enzyme levels suggested potential enhancements in lipid metabolism and liver function. The study also observed modulation of specific proteins related to TMAO production and metabolism, including CutC and CutD. Conclusion The findings highlight the potential of A. muciniphila postbiotics as a dietary strategy for mitigating cardiovascular disease risk by modulating the gut-TMAO axis. Postbiotics, particularly A. muciniphila, offer advantages over probiotics and warrant further investigation for their therapeutic applications in gastrointestinal and metabolic disorders. Graphical Abstract

Abstract Prediabetes is an important stage in the development of diabetes. It is necessary to find a safe, effective and sustainable way to delay and reverse the progression of prediabetes. Akkermansia muciniphila (A. muciniphila) is one of the key bacteria associated with glucose metabolism. Recent studies mainly focus on the effect of A. muciniphila on obesity and insulin resistance, but there is no research on the effect of A. muciniphila on pancreatic β-cell function and its mechanism in prediabetes. In this study, we investigated the effects of A. muciniphila on β-cell function, apoptosis and differentiation, as well as its effects on the gut microbiome, intestinal barrier, metaflammation and the expression of Toll-like receptors (TLRs) in a high-fat diet (HFD)-induced prediabetic rat model. The effect of A. muciniphila was compared with dietary intervention. The results showed both A. muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improve β-cell secretory function, apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4. Additionally, A. muciniphila can further elevate β-cell secretion, attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet.

Extensive research has been conducted to investigate the impact of capsaicin (CAP) on lipid metabolism, focusing specifically on its interaction with the vanilloid subtype 1 (TRPV1) ion channel. Additionally, studies have illuminated the role of Akkermansia muciniphila (A. muciniphila), a specific strain of intestinal microbiota, in lipid metabolism. In this study, a model utilizing resiniferatoxin (RTX) was employed to deactivate TRPV1 ion channels in germ-free mice, followed by the administration of A. muciniphila via gavage. Following the collection of intestinal tissues for a comprehensive analysis, employing histopathology, qPCR, and ELISA techniques, our findings revealed a significant upregulation of MUC2 and MUC3 expression induced by CAP. This upregulation resulted in the thickening of the colonic mucus layers. Notably, this effect was absent when TRPV1 was selectively inhibited. Moreover, there was no discernible impact on goblet cells. The findings strongly indicate that CAP influences the system by activating the TRPV1 ion channel, thereby enhancing the expression of mucin MUC2 and promoting an augmentation in the thickness of the mucous layer. This activation, in turn, supplies A. muciniphila with an ample source of carbon and nitrogen. This insight potentially clarify the underlying mechanism through which CAP facilitates the increase in A. muciniphila abundance.

Akkermansia muciniphila (A. muciniphila), an intestinal symbiont residing in the mucosal layer, shows promise as a probiotic. Our previous study found that the abundance of A. muciniphila was significantly higher in Ningxiang suckling piglets compared to other breeds, suggesting that early breast milk may play a crucial role. This study examines A. muciniphila’s ability to utilize Ningxiang pig milk oligosaccharides. We discovered that A. muciniphila can thrive on both Ningxiang pig colostrum and purified pig milk oligosaccharides. Genetic analysis has shown that A. muciniphila harbors essential glycan-degrading enzymes, enabling it to effectively break down a broad spectrum of oligosaccharides. Our findings demonstrate that A. muciniphila can degrade pig milk oligosaccharides structures such as 3′-FL, 3′-SL, LNT, and LNnT, producing short-chain fatty acids in the process. The hydrolysis of these host-derived glycan structures enhances A. muciniphila’s symbiotic interactions with other beneficial gut bacteria, contributing to a dynamic microbial ecological network. The capability of A. muciniphila to utilize pig milk oligosaccharides allows it to establish itself in the intestines of newborn piglets, effectively colonizing the mucosal layer early in life. This early colonization is key in supporting both mucosal and metabolic health, which is critical for enhancing piglet survival during lactation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Purpose: Panax ginseng is widely applied in the adjuvant treatment of cardiometabolic diseases in clinical practice without clear mechanisms. This study aims to clearly define the efficacy and underlying mechanism of P. ginseng and its active components in protecting against atherosclerosis. Experimental Approach: The anti‐atherogenic efficacy of total ginseng saponin extract (TGS) and its components was evaluated on Ldlr−/− mice. Gut microbial structure was analysed by 16S rRNA sequencing and PCR. Bile acid profiles were revealed using targeted metabolomics with LC–MS/MS analysis. The contribution of gut microbiota to atherosclerosis was assessed by co‐housing experiments. Key Results: Ginsenoside Rb1, representing protopanaxadiol (PPD)‐type saponins, increased intestinal Lactobacillus abundance, resulting in enhanced bile salt hydrolase (BSH) activity to promote intestinal conjugated bile acid hydrolysis and excretion, followed by suppression of enterohepatic farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) signal, and thereby increased cholesterol 7α‐hydroxylase (CYP7A1) transcriptional expression and facilitated metabolic elimination of cholesterol. Synergistically, protopanaxatriol (PPT)‐type saponins, represented by ginsenoside Rg1, protected against atherogenesis‐triggered gut leak and metabolic endotoxaemia. Ginsenoside Rg1 directly induced mucin production to nutritionally maintain Akkermansia muciniphila, which reciprocally inhibited gut permeation. Rb1/Rg1 combination, rather than a single compound, can largely mimic the holistic efficacy of TGS in protecting Ldlr−/− mice from atherogenesis. Conclusion and Implications: Our study provides strong evidence supporting TGS and ginsenoside Rb1/Rg1 combinations as effective therapies against atherogenesis, via targeting different signal nodes by different components and may provide some elucidation of the holistic mode of herbal medicines. [ABSTRACT FROM AUTHOR]

Akkermansia muciniphila (Akk) has recently become popular due to its therapeutic effect on various diseases. However, Akk's high-density cultivation is difficult due to its anaerobic characteristics. Therefore, Akk was cultured with modified brain–heart infusion (M-BHI) to reach 1011 CFU/mL. 1H-NMR determined the metabolites of Akk and validated them by an amino acid analyzer. Compared to the BHI, Akk significantly up-regulated lactate, histidine, fumaric acid, cytidine, threonine, arginine, and hydroxyproline in the M-BHI and significantly down-regulated methionine, trimethylamine, and sarcosine. Regarding pathway enrichment analysis, histidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism mainly regulate differential metabolites. In addition, M-BHI alters the metabolic profile by affecting Akk's involvement in amino acid metabolism remodeling. Changed metabolites showed that Akk fermentation in M-BHI may play a physiological role in regulating immune homeostasis and reducing risk factors related to diseases. Therefore, M-BHI provides a promising reference for Akk cultivation in future industrial preparation. [ABSTRACT FROM AUTHOR]

The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility. Synopsis: Susceptibility to a mucosal pathogen is both microbiome- and diet-dependent, with mucin specialist Akkermansia muciniphila increasing susceptibility on a fiber-free diet, whereas a fiber-rich diet allows the same commensal to confer resistance. Variations of a 14-member synthetic human gut microbiota show the key role of dietary fiber in determining the severity of Citrobacter rodentium infection through specific members of the microbiome. Combined action of increased mucus barrier permeability and altered community networks underlie the increased pathogen susceptibility in the Akkermansia muciniphila-containing communities fed a fiber-free diet. Exclusion of Akkermansia muciniphila from the synthetic microbiota or consumption of a fiber-rich diet is sufficient to prevent severe infection. Dietary context is key, with the presence of Akkermansia muciniphila protecting against severe infection under fiber-rich conditions. Susceptibility to a mucosal pathogen is both microbiome- and diet-dependent, with mucin specialist Akkermansia muciniphila increasing susceptibility on a fiber-free diet, whereas a fiber-rich diet allows the same commensal to confer resistance. [ABSTRACT FROM AUTHOR]

Next-generation microorganisms have recently gained prominence in the scientific community, mainly due to their probiotic and postbiotic potentials. However, there are few studies that investigate these potentials in food allergy models. Therefore, the present study was designed to evaluate the probiotic potential of Akkermansia muciniphila BAA-835 in an ovalbumin food allergy (OVA) model and also analyse possible postbiotic potential. To access the probiotic potential, clinical, immunological, microbiological, and histological parameters were evaluated. In addition, the postbiotic potential was also evaluated by immunological parameters. Treatment with viable A. muciniphila was able to mitigate weight loss and serum levels of IgE and IgG1 anti-OVA in allergic mice. In addition, the ability of the bacteria to reduce the injury of the proximal jejunum, the eosinophil and neutrophil influx, and the levels of eotaxin-1, CXCL1/KC, IL4, IL6, IL9, IL13, IL17, and TNF, was clear. Furthermore, A. muciniphila was able to attenuate dysbiotic signs of food allergy by mitigating Staphylococcus levels and yeast frequency in the gut microbiota. In addition, the administration of the inactivated bacteria attenuated the levels of IgE anti-OVA and eosinophils, indicating its postbiotic effect. Our data demonstrate for the first time that the oral administration of viable and inactivated A. muciniphila BAA-835 promotes a systemic immunomodulatory protective effect in an in vivo model of food allergy to ovalbumin, which suggests its probiotic and postbiotic properties. [ABSTRACT FROM AUTHOR]

Allergic asthma (AA) is a common inflammatory airway disease characterized by increased airway hyper-responsiveness (AHR), inflammation, and remodeling. Akkermansia muciniphila is a strictly anaerobic bacterium residing in the gut and is a promising next-generation probiotic to improve metabolic inflammatory syndrome. A recent study suggested the beneficial effect of live A. muciniphila on allergic airway inflammation (AAI) in mice. However, whether the heatkilled form can improve AAI requires further investigation. Mice sensitized and challenged with house dust mites (HDM) develop AA hallmarks including inflammatory cell infiltration, goblet cell hyperplasia, and subepithelial collagen deposition in the lungs. These phenomena were reversed by oral administration of the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the feces of healthy Koreans. Furthermore, AMDK19-HK diminished the HDM-induced AHR to inhaled methacholine, lung mast cell accumulation, and serum HDM-specific IgE levels. It also led to the overall suppression of IL-4, IL-13, and eotaxin production in bronchoalveolar lavage fluids, and Il4, Il5, Il13, and Ccl17 gene expression in lung tissues. Moreover, AMDK19-HK suppressed Th2-associated cytokine production in the splenocytes of HDM-sensitized mice in vitro. Additionally, a combination of 16S rRNA gene sequencing and shortchain fatty acid (SCFA) analysis in cecal samples revealed that AMDK19-HK modulated the relative abundance of circulating SCFA-associated gut genera, including a positive correlation with Lachnospiraceae_ NK4A136_group and a negative correlation with Lachnoclostridium and significantly increased cecal SCFA concentrations. Finally, AMDK19-HK improved intestinal mucosal barrier function. These results suggest that the oral administration of AMDK19-HK ameliorates HDM-induced AAI in mice by suppressing Th2-mediated immune responses and could have a protective effect against AA development. [ABSTRACT FROM AUTHOR]

Prediabetes is an important stage in the development of diabetes. It is necessary to find a safe, effective and sustainable way to delay and reverse the progression of prediabetes. Akkermansia muciniphila (A. muciniphila) is one of the key bacteria associated with glucose metabolism. Recent studies mainly focus on the effect of A. muciniphila on obesity and insulin resistance, but there is no research on the effect of A. muciniphila on pancreatic β-cell function and its mechanism in prediabetes. In this study, we investigated the effects of A. muciniphila on β-cell function, apoptosis and differentiation, as well as its effects on the gut microbiome, intestinal barrier, metaflammation and the expression of Toll-like receptors (TLRs) in a high-fat diet (HFD)-induced prediabetic rat model. The effect of A. muciniphila was compared with dietary intervention. The results showed both A. muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improve β-cell secretory function, apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4. Additionally, A. muciniphila can further elevate β-cell secretion, attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide. Numerous studies conducted recently have demonstrated a connection between the dysbiosis of the development of NAFLD and gut microbiota. Rebuilding a healthy gut ecology has been proposed as a strategy involving the use of probiotics. The purpose of this work is to investigate and compare the function of probiotics Akkermansia muciniphila (A. muciniphila) and VSL#3 in NAFLD mice. Rodent NAFLD was modeled using a methionine choline-deficient diet (MCD) with/without oral probiotic delivery. Subsequently, qPCR, histological staining, and liver function tests were conducted. Mass spectrometry-based analysis and 16S rDNA gene sequencing were used to investigate the liver metabolome and gut microbiota. We found that while both A. muciniphila and VSL#3 reduced hepatic fat content, A. muciniphila outperformed VSL#3. Furthermore, probiotic treatment restored the β diversity of the gut flora and A. muciniphila decreased the abundance of pathogenic bacteria such as Ileibacterium valens. These probiotics altered the metabolism in MCD mice, especially the glycerophospholipid metabolism. In conclusion, our findings distinguished the role of A. muciniphila and VSL#3 in NAFLD and indicated that oral-gavage probiotics remodel gut microbiota and improve metabolism, raising the possibility of using probiotics in the cure of NAFLD. [ABSTRACT FROM AUTHOR]

The study aims to analyze the composition of the gut microbiota in Chinese individuals using metagenomic sequencing technology, with a particular focus on the abundance of Akkermansia muciniphila (Akk). To improve the efficiency of Akk isolation and identification accuracy, modifications were made to the enrichment culture medium and 16S rRNA universal primers. Additionally, potential growth-promoting factors that stimulate Akk growth were explored through in vitro screening. The research results revealed that the abundance of Akk in Chinese fecal samples ranged from 0.004% to 0.4%. During optimization, a type of animal protein peptide significantly enhanced the enrichment efficiency of Akk, resulting in the isolation of three Akk strains from 14 fecal samples. Furthermore, 17 different growth-promoting factors were compared, and four factors, including galactose, sialic acid, lactose, and chitosan, were identified as significantly promoting Akk growth. Through orthogonal experiments, the optimal ratio of these four growth-promoting factors was determined to be 1:1:2:1. After adding 1.25% of this growth-promoting factor combination to the standard culture medium, Akk was cultivated at 37° for 36 h, achieving an OD600nm value of 1.169, thus realizing efficient proliferation and optimized cultivation of Akk. This study provides important clues for a deeper understanding of the gut microbiota composition in Chinese individuals, while also offering effective methods for the isolation and cultivation of Akk, laying the groundwork for its functional and application research in the human body. [ABSTRACT FROM AUTHOR]

Recent and continuing advances in gut microbiome research have pointed out the role of the gut microbiota as an unexplored source of potentially beneficial probiotic microbes. Along the lines of these advances, both public awareness and acceptance of probiotics are increasing. That's why; academic and industrial research is dedicated to identifying and investigating new microbial strains for the development of next-generation probiotics (NGPs). At this time, there is a growing interest in NGPs as biotherapeutics that alter the gut microbiome and affect various diseases development. In this work, we have focused on some emergent and promising NGPs, specifically Eubacterium hallii, Faecalibacterium prausnitzii, Roseburia spp., Akkermansia muciniphila, and Bacteroides fragilis, as their presence in the gut can have an impact on the development of various diseases. Emerging studies point out the beneficial roles of these NGPs and open up novel promising therapeutic options. Interestingly, these NGPs were found to enhance gastrointestinal immunity, enhance immunotherapy efficacy in cancer patients, retain the intestinal barrier integrity, generate valuable metabolites, especially short-chain fatty acids, and decrease complications of chemotherapy and radiotherapy. Although many of these NGPs are considered promising for the prevention and treatment of several chronic diseases, research on humans is still lacking. Therefore, approval of these microbes from regulatory agencies is rare. Besides, some issues limit their wide use in the market, such as suitable methods for the culture and storage of these oxygen-sensitive microbes. The present review goes over the main points related to NGPs and gives a viewpoint on the key issues that still hinder their wide application. Furthermore, we have focused on the advancement in NGPs and human healthiness investigations by clarifying the limitations of traditional probiotic microorganisms, discussing the characteristics of emerging NGPs and defining their role in the management of certain ailments. Future research should emphasize the isolation, mechanisms of action of these probiotics, safety, and clinical efficacy in humans. [ABSTRACT FROM AUTHOR]

Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Background: Alcoholic liver disease (ALD) is exacerbated by disruptions in intestinal microecology and immune imbalances within the gut-liver axis. The present study assesses the therapeutic potential of combining Akkermansia muciniphila (A. muciniphila) with inosine in alleviating alcohol-induced liver injury. Methods: Male C57BL/6 mice, subjected to a Lieber-DeCarli diet with 5% alcohol for 4 weeks, served as the alcoholic liver injury model. Various analyzes, including quantitative reverse transcription polymerase chain reaction (qRTPCR), ELISA, immunochemistry, 16S rRNA gene sequencing, and flow cytometry, were employed to evaluate liver injury parameters, intestinal barrier function, microbiota composition, and immune responses. Results: Compared to the model group, the A. muciniphila and inosine groups exhibited significantly decreased alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide (LPS) levels, reduced hepatic fat deposition and neutrophil infiltration, alleviated oxidative stress and inflammation, and increased expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). These effects were further pronounced in the A. muciniphila and inosine combination group compared to individual treatments. While alcohol feeding induced intestinal dysbiosis and gut barrier disruption, the combined treatment reduced the abundance of harmful bacteria (Oscillibacter, Escherichia/Shigella, and Alistipes) induced by alcohol consumption, promoting the growth of butyrate-producing bacteria (Akkermansia, Lactobacillus, and Clostridium IV). Flow cytometry revealed that alcohol consumption reduced T regulatory (Treg) populations while increasing those of T-helper (Th) 1 and Th17, which were restored by A. muciniphila combined with inosine treatment. Moreover, A. muciniphila and inosine combination increased the expression levels of intestinal CD39, CD73, and adenosine A2A receptor (A2AR) along with enhanced proportions of CD4+CD39+Treg and CD4+CD73+Treg cells in the liver and spleen. The A2AR antagonist KW6002, blocked the beneficial effects of the A. muciniphila and inosine combination on liver injury in ALD mice. Conclusion: This study reveals that the combination of A. muciniphila and inosine holds promise for ameliorating ALD by enhancing the gut ecosystem, improving intestinal barrier function, upregulating A2AR, CD73, and CD39 expression, modulating Treg cells functionality, and regulating the imbalance of Treg/Th17/Th1 cells, and these beneficial effects are partly A2AR-dependent. [ABSTRACT FROM AUTHOR]

Probiotics play a crucial role in immunomodulation by regulating dendritic cell (DC) maturation and inducing tolerogenic DCs. Akkermansia muciniphila affects inflammatory response by elevating inhibitory cytokines. We aimed to evaluate whether Akkermansia muciniphila and its outer membrane vesicles (OMVs) affect microRNA-155, microRNA-146a, microRNA-34a, and let-7i expression of inflammatory and anti-inflammatory pathways. Peripheral blood mononuclear cells (PBMCs) were isolated from the healthy volunteers. To produce DCs, monocytes were cultivated with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were allocated into six subgroups: DC + Lipopolysaccharide (LPS), DC + dexamethasone, DC + A. muciniphila (MOI 100, 50), DC + OMVs (50 µg/ml), and DC + PBS. The surface expression of human leukocyte antigen-antigen D related (HLA-DR), CD86, CD80, CD83, CD11c, and CD14 was examined using flow cytometry, and the expression of microRNAs was assessed using qRT-PCR, and the levels of IL-12 and IL-10 were measured using ELISA. A. muciniphila (MOIs 50, 100) could significantly decrease IL-12 levels relative to the LPS group. The IL-10 levels were decreased in the DC + LPS group than the DC + dexamethasone group. Treatment with A. muciniphila (MOI 100) and OMVs could elevate the concentrations of IL-10. DC treatment with LPS led to a significant increment in the expression of microRNA-155, microRNA-34a, and microRNA-146a. The expression of these microRNAs was reversed by A. muciniphilia and its OMVs treatment. Let-7i increased in treatment groups compared to the DC + LPS group. A. muciniphilia (MOI 50) had a substantial effect on the expression of HLA-DR, CD80, and CD83 on DCs. Therefore, DCs treatment with A. muciniphila led to induce tolerogenic DCs and the production of anti-inflammatory IL-10. [ABSTRACT FROM AUTHOR]

Adequate bone development is imperative for maintaining the health and productivity of laying hens. Probiotics play a pivotal role in promoting bone formation and preventing osteoporosis. This study aimed to explore the effect of Akkermansia muciniphila (Akk) on the bone development and eggshell quality of laying hens during the rearing period. A total of 300 1-day-old Jingfen NO. 6 commercial pullets were categorized into two groups, one of which was fed a conventional diet for 20 weeks (Control group), the other group was fed a conventional diet with lyophilized Akk powder for 20 weeks (Akk group). During the first two weeks, pullets in the Akk group received live Akk inoculation, while birds in the Control group received normal saline administration. Micro-computed tomography analysis was employed to evaluate three bone microarchitectures: cortical bone (Cb), trabecular bone (Tb), and medullary bone (Mb). Our findings revealed that supplementation with Akk powder increased the thickness and bone mineral content of Cb and Tb, while simultaneously reducing the volume and bone surface area of Mb. The increased activity of alkaline phosphatase, a marker of osteogenesis, and the decreased activity of tartrate-resistant acid phosphatase, a marker of osteoclastic activity, were observed in the Akk group. Dietary supplementation of Akk powder improved the immune microenvironment in the bone marrow by increasing osteogenic-related CD8+ T cells and decreasing osteoclastogenesis-related CD4+ T cells. Additionally, Akk powder supplementation significantly enriched the Lactobacillaceae family in cecum. The enhancement of bone development by Akk contributed to increased eggshell strength and thickness. These findings demonstrate the osteomodulatory effects of Akk in laying hens and the connections between bone physiology and eggshell quality, highlighting the importance of gut–bone communications in laying hens. [ABSTRACT FROM AUTHOR]

This study examined the effects of an extract of the green algae Codium fragile (hereafter referred to as CFE) on dextran sulfate sodium (DSS)-induced colitis. As the administration of CFE increased, the proliferation of Akkermansia muciniphila, which is a key player in metabolic and gastrointestinal disorders, also increased. After CFE administration for 10 weeks, acetic acid was identified as the major metabolite in mouse cecum and β-glucuronidase activity in mouse fecesdecreased. Further, CFE significantly alleviated the acute intestinal injury induced by DSS administration, including DAI score, colon length, and histological score. The experimental group also displayed indications of significantly lower neutrophil activity and inflammation. In conclusion, the protective effect of CFE against DSS colitis suggests its clinical use by IBD patients. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the effects of berberine (BBR) as a treatment on intestinal microecological alterations and enteritis in mice produced by TNBS.MethodsThere were seven mice per group: seven in the healthy group (Ctrl), seven in the TNBS-induced enteritis group (TNBS), and seven in the berberine treatment group (BBR). The mice were weighed, slaughtered after 7 days, and subjected to high-throughput intestinal microecological analysis by Illumina, as well as haematological detection and imaging evaluation of colon pathology.ResultsThe alterations in colon length, immune cell subpopulations, inflammatory factors, and intestinal microecology of mice induced by BBR were refined using a battery of experiments and observations. According to intestinal microecological studies, BBR can increase the number of bacteria, including Lactobacillus, Verrucomicrobia, Bacteroides, and Akkermansia muciniphila.ConclusionBBR has a therapeutic effect on TNBS-induced colitis in mice, which is associated with modifications in immune cell subpopulations and intestinal microecology. It also offers a viable approach as a prospective probiotic (like Akkermansia muciniphila) to IBD therapy in clinical settings.

Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.

Abstract The qualified presumption of safety (QPS) process was developed to provide a safety assessment approach for microorganisms intended for use in food or feed chains. In the period covered by this statement, no new information was found that would change the status of previously recommended QPS TUs. The TUs in the QPS list were updated based on a verification, against their respective authoritative databases, of the correctness of the names and completeness of synonyms. A new procedure has been established to ensure the TUs are kept up to date in relation to recent taxonomical insights. Of 81 microorganisms notified to EFSA between October 2023 and March 2024 (45 as feed additives, 25 as food enzymes or additives, 11 as novel foods), 75 were not evaluated because: 15 were filamentous fungi, 1 was Enterococcus faecium, 10 were Escherichia coli, 1 was a Streptomyces (all excluded from the QPS evaluation) and 46 were TUs that already have a QPS status. Two of the other eight notifications were already evaluated for a possible QPS status in the previous Panel Statement: Heyndrickxia faecalis (previously Weizmannia faecalis) and Serratia marcescens. One was notified at genus level so could not be assessed for QPS status. The other five notifications belonging to five TUs were assessed for possible QPS status. Akkermansia muciniphila and Actinomadura roseirufa were still not recommended for QPS status due to safety concerns. Rhizobium radiobacter can be recommended for QPS status with the qualification for production purposes. Microbacterium arborescens and Burkholderia stagnalis cannot be included in the QPS list due to a lack of body of knowledge for its use in the food and feed chain and for B. stagnalis also due to safety concerns. A. roseirufa and B. stagnalis have been excluded from further QPS assessment.

Abstract Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota‐derived 3‐hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6‐mediated radiation damage. Irradiated cell‐fecal microbiota co‐culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43‐mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut‐immune axis in radiation pathophysiology, with potential therapeutic applications.

IntroductionUlcerative colitis is an inflammatory disorder characterized by chronic inflammation in the gastrointestinal tract, mainly in the colon and rectum. Although the precise etiology of ulcerative colitis remains unclear, recent research has underscored the significant role of the microbiome in its development and progression.MethodsThe aim of this study was to establish a relationship between the levels of specific gut bacterial species and disease relapse in ulcerative colitis. For this study, we recruited 105 ulcerative colitis patients in remission and collected clinical data, blood, and stool samples. Akkermansia muciniphila and Parabacteroides distasonis levels were quantified in the stool samples of ulcerative colitis patients. Binary logistic regression was applied to collected data to predict disease remission.ResultsThe median time in remission in this cohort was four years. A predictive model incorporating demographic information, clinical data, and the levels of Akkermansia muciniphila and Parabacteroides distasonis was developed to understand remission patterns.DiscussionOur findings revealed a negative correlation between the levels of these two microorganisms and the duration of remission. These findings highlight the importance of the gut microbiota in ulcerative colitis for disease prognosis and for personalized treatments based on microbiome interventions.

Abstract As one of the most attractive next‐generation probiotics, mucin‐degrading Akkermansia muciniphila has emerged as an essential and integral factor in maintaining human health and affecting pathological outcomes. Its abundance is inversely associated with various metabolic diseases (e.g., obesity and type 2 diabetes), cardiovascular diseases, and intestinal inflammation. Supplementing A. muciniphila to restore the gut microbiota ecosystem is a promising approach for treating metabolic disorders. However, the direct utilization of this probiotic is limited by technological and regulatory hurdles, such as the in vitro bulk culture of A. muciniphila and the need for expensive animal‐derived materials. Therefore, enrichment of A. muciniphila using nutraceutical supplements is a feasible strategy. Dietary supplements, especially medicinal herbs, offer a vast and valuable resource as potential prebiotics for promoting the growth of A. muciniphila in the gut, ensuring reliable safety and efficacy. In this study, we first systemically reviewed the dietary substances and medicinal foods known to promote A. muciniphila from over 100 literature sources, aiming to establish a candidate basis for future exploration of prebiotics targeting A. muciniphila. Furthermore, we summarized and discussed the major regulatory factors and mechanisms responsible for the beneficial effect of A. muciniphila on metabolic disorders, hoping to open up exciting directions for in‐depth research on the pharmacological mechanism of A. muciniphila and pave the way for its clinical therapeutics.

Akkermansia muciniphila play an important in ameliorating obesity but is not allowed for direct consumption in most countries. To date, microbiota-directed foods selectively promote the targeted human gut microbes, providing a strategy for A. muciniphila enhancement. Multiple studies have indicated the potential regulation of the polyphenol on A. muciniphila. Therefore, a polyphenol screening based on A. muciniphila upregulation was performed in mice. Chlorogenic acid (CGA) exhibited a greater response to A. muciniphila upregulation. Furthermore, we found that CGA did not directly promote A. muciniphila growth or mucin secretion. Microbiome and metabolomics revealed that the increased abundance of A. muciniphila resulted from the inhibition of CGA on Desulfovibrio and Alistipes and the influence of docosahexaenoic acid, β-hydroxybutyrate, and N-acetyl-lactosamine. Finally, to confirm the regulation of CGA on A. muciniphila under disease conditions, high-fat diet-fed mice were established. The results showed CGA promoted A. muciniphila growth, and we expectedly found that CGA suppressed the augment in body weight of mice, significantly attenuated adipose tissue abnormality, provided liver protection and improved gut barrier integrity. These results suggest that CGA inhibits the development of obesity. Overall, our results indicate that microbiota-directed food is a promising approach for the treatment of obesity.

Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, A. muciniphila regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of A. muciniphila are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live A. muciniphila, but also in pasteurized A. muciniphila, A. muciniphila-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and A. muciniphila, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of A. muciniphila on different diseases and summarize the potential mechanisms of action of A. muciniphila in the treatment of diseases. We provide a comprehensive understanding of A. muciniphila for improving host health and discuss the perspectives of A. muciniphila in the future studies.

ABSTRACTThe gut microbiota has coevolved with the host for hundreds of millions of years, playing a beneficial role in host health. Human parasitic helminths are widespread and pose a pervasive global public health issue. Although Type 2 immunity provides partial resistance to helminth infections, the composition of the gut microbiota can change correspondingly. Therefore, it raises the question of what role the gut microbiota plays during helminth infection. Akkermansia muciniphila has emerged as a notable representative of beneficial microorganisms in the gut microbiota. Recent studies indicate that A. muciniphila is not merely associated with helminth infection but is also causally linked to infection. Here, we provide an overview of the crosstalk between A. muciniphila and enteric helminth infection. Our goal is to enhance our understanding of the interplay among A. muciniphila, helminths, and their hosts while also exploring the potential underlying mechanisms.

Obesity is caused by an energy imbalance and leads to metabolic syndrome and diseases. The gut microbiota, influenced by diet, crucially impacts obesity. Kimchi, a traditional Korean fermented food rich in lactic acid bacteria, may alter gut microbiota composition. This randomized, double-blind, placebo-controlled trial enrolled 90 participants (BMI 23–30 kg/m2) to investigate the anti-obesity effects of kimchi. Participants consumed 3000 mg of spontaneously fermented kimchi powder (S-K) or starter-fermented kimchi powder with Leuconostoc mesenteroides KCKM0828 (LMS-K) daily for 12 weeks, while the placebo group consumed lactose. Both the S-K and LMS-K groups exhibited a significant reduction in body fat mass compared to the placebo group (S-K: p = 0.004, LMS-K: p = 0.003). Kimchi consumption also increased the proportion of Akkermansia muciniphila while decreasing that of Proteobacteria. Cumulatively, these findings suggest that daily kimchi consumption may alleviate obesity symptoms by regulating gut microbiota.