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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.

In mice with acute gouty arthritis, this study intends to examine the mechanism of action of Akkermansia muciniphila AKK PROBIO. We developed a mouse model of acute gouty arthritis using sodium urate. The efficiency and mechanism of AKK PROBIO in preventing acute gouty arthritis in mice were then determined by examining the degree of foot swelling, pain threshold, blood biochemical indicators, histological alterations, and messenger RNA (mRNA) expression changes. The results of the animal experiment showed that AKK PROBIO can lessen mouse foot edema severity and increase pain threshold. AKK PROBIO can enhance the enzyme activity of superoxide dismutase (SOD) and the level of glutathione (GSH) in the ankle joint tissues of mice with acute arthritis while decreasing the enzyme activity of myeloperoxidase (MPO) and the level of malondialdehyde (MDA). Interleukin 6 (IL‐6), interleukin 10 (IL‐10), interleukin 1 beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α) levels are all reduced by AKK PROBIO in the blood of mice with acute arthritis. Results from histopathology showed that AKK PROBIO reduced tissue damage in the mouse ankle and foot joints. In the tissues of the ankle joints of mice with acute arthritis, the results of the quantitative polymerase chain reaction (qPCR) and Western blot experiments suggested that AKK PROBIO may inhibit the mRNA and protein expression of extracellular signal‐regulated kinase 1/2 (ERK1/2), cyclooxygenase‐2 (COX‐2), and prostaglandin E2 (PGE2) in the tissues. AKK PROBIO can also regulate gut microbiota, inhibit harmful bacteria, and enhance valeric acid in the intestine, isobutyric acid, and isovaleric acid. Therefore, it is evident that AKK PROBIO prevents acute gouty arthritis better than glucosamine sulfate. It is a strain that has probiotic potential. [ABSTRACT FROM AUTHOR]

Backrground: Akkermansia muciniphila, a next-generation probiotic, is known as a cornerstone regulating the gut-organ axis in various diseases, but the underlying mechanism remains poorly understood. Here, we revealed the neuronal and antifibrotic effects of A. muciniphila on the gut-liver-brain axis in liver injury. Results: To investigate neurologic dysfunction and characteristic gut microbiotas, we performed a cirrhosis cohort (154 patients with or without hepatic encephalopathy) and a community cognition cohort (80 participants in one region for three years) and validated the existence of cognitive impairment in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic injury mouse model. The effects of the candidate strain on cognition were evaluated in animal models of liver injury. The expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors was accessed in patients with fibrosis (100 patients) according to the fibrosis grade and hepatic venous pressure gradient. The proportion of A. muciniphila decreased in populations with hepatic encephalopathy and cognitive dysfunction. Tissue staining techniques confirmed gut-liver-brain damage in liver injury, with drastic expression of BDNF and serotonin in the gut and brain. The administration of A. muciniphila significantly reduced tissue damage and improved cognitive dysfunction and the expression of BDNF and serotonin. Isolated vagus nerve staining showed a recovery of serotonin expression without affecting the dopamine pathway. Conversely, in liver tissue, the inhibition of injury through the suppression of serotonin receptor (5-hydroxytryptamine 2A and 2B) expression was confirmed. The severity of liver injury was correlated with the abundance of serotonin, BDNF, and A. muciniphila. Conclusions: A. muciniphila, a next-generation probiotic, is a therapeutic candidate for alleviating the symptoms of liver fibrosis and cognitive impairment. [ABSTRACT FROM AUTHOR]

The oral microbiome is a diverse ecosystem containing a community of symbiotic, commensal, and pathogenic microorganisms. One key microorganism linked to periodontal disease (PD) is Porphyromonas gingivalis (P. gingivalis), a Gram-negative anaerobic bacterium known to have several virulence factors that trigger inflammation and immune evasion. On the other hand, Akkermansia muciniphila (A. muciniphila), a symbiotic bacterium, has been recently shown to play an important role in mitigating inflammation and reducing periodontal damage. In vivo and in vitro studies have shown that A. muciniphila decreases inflammatory mediators and improves immune responses, suggesting its role in mitigating PD and related inflammatory systemic conditions such as diabetes, hypertension, and obesity. This review discusses the anti-inflammatory effects of A. muciniphila, its impact on periodontal health, and its potential role in managing systemic diseases. The overall aim is to elucidate how this bacterium might help reduce inflammation, improve oral health, and influence broader health outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of berberine (BBR) as a treatment on intestinal microecological alterations and enteritis in mice produced by TNBS. Methods: There 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. Results: The 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. Conclusion: BBR 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. [ABSTRACT FROM AUTHOR]

A substantial body of research indicates that the gut microbiota exerts a profound influence on host health. The purpose of this work was to characterize selected, most promising, well-known next-generation probiotics (NGPs) and review the potential applications of the bacteria in food technology. The isolation of gut bacteria with significant health benefits has led to the emergence of NGPs. In contrast to traditional probiotics, these originate directly from the gut microbiota, thereby ensuring their optimal adaptation to the intestinal ecosystem. NGPs exert their effects on the host organism through a variety of mechanisms, including the synthesis of bioactive compounds, modulation of the gut microbiota, and metabolism of substances provided by the host. Several bacterial species have been identified as potential candidates for NGPs, including Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Christensenella minuta, and many others. These bacteria have demonstrated the capacity to exert beneficial effects, including the reduction of obesity, type 2 diabetes, metabolic disorders, and even cancers. The greatest limitation to their commercialization is their lack of oxygen tolerance, which presents challenges not only for research but also for their potential application in food. The most optimal approach for their application in food appears to be microencapsulation. Further research is required to establish the safety of NGP supplementation and to protect them from environmental conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Endometriosis, affecting 10% of women in their reproductive years, remains poorly understood. Both individual and environmental unexplained factors are implicated in this heterogenous condition. This study aims to examine the influence of a Western diet on endometriosis lesion development in mice and to uncover the mechanisms involved. Methods Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4 weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7 weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing. Results Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota. Conclusions A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development. Graphical Abstract

Abstract Backrground Akkermansia muciniphila, a next-generation probiotic, is known as a cornerstone regulating the gut-organ axis in various diseases, but the underlying mechanism remains poorly understood. Here, we revealed the neuronal and antifibrotic effects of A. muciniphila on the gut-liver-brain axis in liver injury. Results To investigate neurologic dysfunction and characteristic gut microbiotas, we performed a cirrhosis cohort (154 patients with or without hepatic encephalopathy) and a community cognition cohort (80 participants in one region for three years) and validated the existence of cognitive impairment in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic injury mouse model. The effects of the candidate strain on cognition were evaluated in animal models of liver injury. The expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors was accessed in patients with fibrosis (100 patients) according to the fibrosis grade and hepatic venous pressure gradient. The proportion of A. muciniphila decreased in populations with hepatic encephalopathy and cognitive dysfunction. Tissue staining techniques confirmed gut-liver-brain damage in liver injury, with drastic expression of BDNF and serotonin in the gut and brain. The administration of A. muciniphila significantly reduced tissue damage and improved cognitive dysfunction and the expression of BDNF and serotonin. Isolated vagus nerve staining showed a recovery of serotonin expression without affecting the dopamine pathway. Conversely, in liver tissue, the inhibition of injury through the suppression of serotonin receptor (5-hydroxytryptamine 2A and 2B) expression was confirmed. The severity of liver injury was correlated with the abundance of serotonin, BDNF, and A. muciniphila. Conclusions A. muciniphila, a next-generation probiotic, is a therapeutic candidate for alleviating the symptoms of liver fibrosis and cognitive impairment. Graphical 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. [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.

Akkermansia muciniphila is a Gram-negative anaerobic bacterium, a component of the normal human intestinal microbiota. A decrease in the presence of this bacterium is associated with pathologies, including metabolic disorders, intestinal inflammation and colorectal cancer. A. muciniphila is a probiotic approved for patients with diabetes and obesity. In recent years, A. muciniphila was studied in the control of intestinal inflammation and colorectal cancer. The exact mechanisms of A. muciniphila action remain unclear, while the use of different administration protocols shows different effects in mouse models of colitis and colorectal cancer. We reported that A. muciniphila has distinct effects on intestinal mucin production depending on viable or pasteurized form of bacteria. Another factor affecting the outcome of the A. muciniphila administration is the number of bacteria. To address how the dose of bacteria may affect the severity of acute intestinal inflammation wild-type mice were subjected to daily oral injections with 10⁸ CFU or 109 CFU of viable A. muciniphila for two weeks; the control group was injected with PBS. After that, groups were subjected to the induction of acute colitis by adding 7% DSS to drinking water for five days. 8 days after the onset of colitis induction, a morphometric assessment of the colitis severity was performed. Mice given a high dose of A. muciniphila (109 CFU) were found to be protected from developing severe colitis. RT-PCR analysis of colon samples from mice receiving a high dose of bacteria showed an increase in the gene expression of antimicrobial peptides, IL-17A, IL-17F. Interestingly, the protective effect of A. muciniphila was observed only in a high dose group, but not in a low dose group. Our data suggest that A. muciniphila provides the protective effect in colitis and highlight the importance of selecting the dose of the bacterium for proper interpretation.

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

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]

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]

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]

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]

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]

Contemporary scientific discussions are increasingly focusing on Akkermansia muciniphila due to its complex influence on intestinal physiology. This article provides a comprehensive analysis of the various effects Akkermansia muciniphila has on intestinal inflammation, while also exploring its potential associations with obesity and cardiovascular diseases. A systematic literature search was conducted using PubMed, Google Scholar, and ResearchGate with the following keywords: Akkermansia muciniphila, obesity, cardiovascular risk, and inflammatory bowel diseases. The aim of our mini-review was to examine the impact of Akkermansia bacteria on the intestines, cardiovascular system, and its relationship with obesity. Through a detailed review of current literature, the article seeks to elucidate the complex interactions of Akkermansia muciniphila within the human body, highlighting its potential contributions to health improvement and medical interventions. Research indicates that Akkermansia muciniphila positively correlates with maintaining intestinal health, modulating the cardiovascular system, and aiding in weight management. However, the number of studies available is small, and the effects of Akkermansia muciniphila on human health require further research.

According to the FAO/WHO guidelines, selection of probiotics requires the assessment of survival under gastrointestinal stress and adhesion to human epithelial cells. These attributes were evaluated on Akkermansia muciniphila ATCC BAA-835 simulating the gastrointestinal transit (GIT) immediately followed by adhesion to human intestinal cell lines (CaCo2, HT-29, and HT-29-MTX) as an alternative approach to in vitro methods performed with fresh cells in each trial. The survival rate after GIT, as determined by plate counts and fluorescent probes, was significantly higher for A. muciniphila (about 8 Log CFU/mL) than for the probiotic Lacticaseibacillus rhamnosus GG ATCC 53103 (about 3 Log CFU/mL). The use of Live/Dead assay highlighted that A. muciniphila forms cell aggregates in the gastric phase as protective mechanism, explaining its high viability in the intestine. The rate of adhesion to human cell lines was always lower for strains tested after simulated GIT than for strains that did not undergo simulated GIT. Akkermansia muciniphila exhibited significantly higher adhesion than Lbs. rhamnosus GG, particularly to the mucus-secreting HT-29-MTX cells across a range of concentrations (2–8 Log CFU/mL). Finally, the bioinformatic analysis of A. muciniphila proteome confirmed the Amuc_1434 as a potential factor in binding to the human MUC2 protein.

Pulmonary fibrosis (PF) is a progressive and debilitating respiratory condition characterized by excessive deposition of extracellular matrix proteins and scarring within the lung parenchyma. Despite extensive research, the pathogenesis of PF remains incompletely understood, and effective therapeutic options are limited. Emerging evidence suggests a potential link between gut microbiota dysbiosis and the development of PF, highlighting the gut-lung axis as a promising therapeutic target. Akkermansia muciniphila (A. muciniphila), a mucin-degrading bacterium residing in the gut mucosal layer, has garnered considerable interest due to its immunomodulatory and anti-inflammatory properties. This study investigates the therapeutic potential of live and pasteurized A. muciniphila, as well as its extracellular vesicles (EVs), in mitigating inflammation and fibrosis in a murine model of carbon tetrachloride (CCl4)-induced PF exacerbated by a high-fat diet (HFD).Male C57BL/6 mice were divided into groups receiving either a normal diet or an HFD, with or without CCl4 administration. The mice were then treated with live or pasteurized A. muciniphila, or its EVs. Lung tissue was analyzed for the expression of inflammatory markers and fibrosis markers using real-time PCR and ELISA.Administration of live and pasteurized A. muciniphila, as well as its EVs, significantly downregulated the expression of inflammatory and fibrosis markers in the lung tissue of CCl4-induced PF mice. Furthermore, these treatments ameliorated the increased production of IL-6 and reduced IL-10 levels observed in the HFD and CCl4-treated groups.These findings suggest that A. muciniphila and its derivatives exert protective effects against pulmonary inflammation and fibrosis, potentially through modulation of the gut-lung axis. The study highlights the therapeutic potential of A. muciniphila and its derivatives as novel interventions for the management of PF, warranting further preclinical and clinical investigations.

Akkermansia muciniphila (Akk) is an important probiotic that can help alleviate metabolic disorders. Recent research indicates that pasteurized Akkermansia muciniphila (P-Akk) is even more effective. To investigate the effect of P-Akk on improving lipid metabolism disorders caused by a high-fat diet (HFD) in fish, zebrafish were fed two HFDs containing 0 (HFD group, as control) and 1 × 109 CFU/g P-Akk (P-Akk group) for 28 days. The addition of P-Akk significantly decreased the number of lipid droplets in the liver and improved the mitochondrial structure in the intestine, while also altering gene expression related to lipid metabolism in HFD-fed zebrafish. Furthermore, intestinal transcriptomic network analysis and results from primary intestinal cells indicated that P-Akk may enhance mitochondrial function by activating the AMPK/PGC1α pathway. Although P-Akk did not significantly alter the composition of the gut microbiota, it did increase the steady-state index of intestinal microbiota. Moreover, P-Akk upregulated the abundance of beneficial probiotics, (Plesiomonas, Cetobacterium, and Bacillus), while downregulating the abundance of pathogens (Aeromonas, Pseudomonas, Acinetobacter, and Streptococcus). Collectively, these findings indicate that P-Akk has the potential to serve as a green and safe feed additive for improving HFD-induced lipid metabolism disorders in fish.

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.

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.

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.

Gut microbiome plays a pivotal role in combating diseases and facilitating healthy aging, and natural products derived from biosynthetic gene clusters (BGCs) of the human microbiome exhibit significant biological activities. However, the natural products of the gut microbiome in long-lived populations remain poorly understood. Here, we integrated six cohorts of long-lived populations, encompassing a total of 1029 fecal metagenomic samples, and employed the metagenomic single sample assembled BGCs (MSSA-BGCs) analysis pipeline to investigate the natural products and their associated species. Our findings reveal that the BGC composition of the extremely long-lived group differed significantly from that of younger elderly and young individuals across five cohorts. Terpene and Type I PKS BGCs were enriched in the extremely long-lived, whereas cyclic-lactone-autoinducer BGCs were more prevalent in the young. Association analysis indicated that terpene BGCs were strongly associated with the abundance of Akkermansia muciniphila, which was also more abundant in the long-lived elderly across at least three cohorts. We assembled 18 A. muciniphila draft genomes using metagenomic data from the extremely long-lived group across six cohorts and discovered that they all harbor two classes of terpene BGCs, which aligns with the 97 complete genomes of A. muciniphila strains retrieved from the NCBI database. The core domains of these two BGC classes are squalene/phytoene synthases involved in the biosynthesis of tri- and tetraterpenes. Furthermore, the abundance of fecal A. muciniphila was significantly associated with eight types of triterpenoids. Targeted terpenoid metabolomic analysis revealed that two triterpenoids, Holstinone C and colubrinic acid, were enriched in the A. muciniphila culture solution compared to the medium, thereby confirming the production of triterpenoids by A. muciniphila. The natural products derived from the gut of long-lived populations provide intriguing indications of their potential beneficial roles in regulating health.

A powder formulation of viable Akkermansia muciniphila bacteria (AMUC) was evaluated in a 90-day repeated-dose toxicity study in rats and a battery of genotoxicity studies to evaluate AMUC as a food ingredient. All studies followed Organisation for Economic Co-operation and Development protocols (OECD TG 408, 471 473, 474). AMUC was administered to rats via gavage at 0, 500, 1000, and 2000 mg/kg body weight/day (equivalent to 0, 4.1 × 1010, 9.2 × 1010, and 1.64 × 1011 CFU/kg body weight/day). No mortality or treatment-related adverse effects were reported in any endpoints that were attributed to AMUC consumption. No bacterial translocation of viable A. muciniphila from the intestinal tract was found to the liver, mesenteric lymph nodes, or blood. The no-observed-adverse-effect level was concluded to be the highest dose tested (2000 mg/kg body weight/day), approximately 1.64 × 1011 CFU/kg body weight/day. AMUC (nonviable) was not mutagenic when examined in an in vitro bacterial reverse mutation assay and not clastogenic in an in vitro mammalian chromosomal aberration test. Viable AMUC was not genotoxic when evaluated in an in vivo mammalian cell micronucleus assay when administered at up to 1.64 ×1011 CFU/kg body weight/day. These results confirm that AMUC is not toxic under the conditions of these studies.

Akkermansia sp are common members of the human gut microbiota. Multiple reports have emerged linking the abundance of A. muciniphila to health benefits and disease risk in humans and animals. This review highlights findings linking Akkermansia species in the gastrointestinal (GI) tract to health outcomes across a spectrum of disorders, encompassing those that affect the digestive, respiratory, urinary, and central nervous systems. The mechanism through which Akkermansia exerts a beneficial versus a detrimental effect on health is likely dependent on the genetic makeup of the host metabolic capacity and immunomodulatory properties of the strain, the competition or cooperation with other members of the host microbiota, as well as synergy with co-administered therapies.

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.

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]

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]

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]

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]

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]

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson's disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy. [ABSTRACT FROM AUTHOR]

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.