Akkermansia muciniphila

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder linked to insulin resistance and hyperandrogenism. Gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs), indoles, and bile acids, influence endocrine and metabolic pathways. Yet, no systematic review has specifically examined metabolite-targeted interventions in PCOS. OBJECTIVE: To assess the effects of probiotic-derived metabolite interventions on hormonal and metabolic outcomes in women with PCOS. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD42025543210), we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and two Chinese databases to May 2025 without language restrictions. Eligible studies were randomized or quasi-randomized controlled trials ≥8 weeks. Two reviewers independently screened, extracted data, and assessed risk of bias (RoB 2). Pooled analyses used random-effects models, and evidence certainty was appraised with GRADE. RESULTS: Seventeen trials (n = 1, 214 women) were included, testing synbiotics (6), probiotics (7), sodium butyrate (2), Akkermansia muciniphila (1), and an SCFA blend (1). Interventions significantly reduced total testosterone (MD -0.19 ng/mL, 95% CI -0.30 to -0.08), LH/FSH ratio (SMD -0.46; 95% CI -0.66 to -0.26), fasting insulin (MD -2.4 µIU/mL; 95% CI -3.9 to -0.9), and HOMA-IR (MD -0.49; 95% CI -0.78 to -0.19). HDL-C increased modestly (MD + 3.2 mg/dL; 95% CI + 0.7 to +5.6). Evidence certainty was moderate for insulin-related outcomes and low for sex-hormone outcomes. CONCLUSION: STargeting gut-derived metabolites, particularly with sodium butyrate and multi-strain synbiotics, improves hormonal and metabolic markers in PCOS. Larger multicenter RCTs with metabolomic confirmation are warranted to establish clinical translation. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42025543210.

The gut microbiota has emerged as a critical determinant of antitumor immunity and a potential modulator of responses to immune checkpoint inhibitors (ICIs). Although pre-clinical and clinical studies suggest that specific bacterial taxa may influence both efficacy and immune-related adverse events (irAEs). However, the magnitude and consistency of these associations remain unclear. A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted through March 2025. Eligible studies evaluated baseline gut microbiota composition, fecal microbiota transplantation (FMT), probiotic/prebiotic interventions, or antibiotic exposure in cancer patients treated with ICIs. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for response rates and irAEs, were estimated using random-effects models. Across 38 studies involving 5,642 patients were included. Pooled analysis demonstrated that enrichment of Akkermansia muciniphila, Bifidobacterium longum and Faecalibacterium prausnitzii was significantly associated with improved OS (HR 0.62, 95% CI 0.51-0.76) and PFS (HR 0.69, 95% CI 0.55-0.83). Conversely, antibiotic exposure before or during ICI treatment was associated with worse OS (HR 1.84, 95% CI 1.45-2.34). Patients undergoing FMT from responders exhibited higher objective response rates (OR 2.91, 95% CI 1.48-5.73). Microbiota diversity indices were consistently higher in responders than in non-responders. Collectively, gut microbiota composition and its modulation significantly impact the therapeutic efficacy and toxicity profile of ICIs. These findings highlight the translational potential of microbiome-based biomarkers and interventions in optimizing immunotherapy.

BACKGROUND: Akkermansia muciniphila (A. muciniphila), a bacterial species within the human gut microbiome, has shown beneficial effects on host health. Emerging research suggests that A. muciniphila also influences neurobehavioral domains through the microbiota-gut-brain axis. This meta-analysis evaluates A. muciniphila's impact on depression, anxiety, and stress in mouse models. METHODS: We conducted a systematic search of PubMed, Science Direct, Embase, and Web of Science databases up to March 2024, identifying 15 eligible studies. RESULTS: Supplementation with A. muciniphila, its outer membrane protein (Amuc_1100), and extracellular vesicles (EVs) alleviated anxiety, depressive-like behaviors, and enhanced memory in mice. Compared to controls, intervention groups exhibited reduced anxiety-like behaviors, including increased travel distance in the open-field test (OFT) and more time spent in the lightbox during the light-dark box (LDB) test and open arms in the elevated plus maze (EPM). Depression-like symptoms were reduced, with lower immobility time in the tail suspension and forced swim tests. Memory function also improved, and learning time was reduced in the Y-maze and Barnes circular maze tests. Serotonin levels increased significantly in the serum and hippocampus, while corticosterone levels decreased, though not significantly. The intervention reduced hippocampal and serum inflammatory markers (TNFα, IL1β, IL6) and altered gut microbiome composition, increasing Akkermansia, Roseburia, Caldicoprobacter, and Lachnospiraceae. CONCLUSION: This meta-analysis provides evidence supporting the health-promoting effects of A. muciniphila, one of the next-generation probiotics, in alleviating neuropsychiatric disorders. Given the high prevalence and clinical significance of depression, anxiety, and stress, further investigation into the therapeutic utility of A. muciniphila is warranted.

BACKGROUND: More than half of the states in the U.S. report that over 30% of adults are obese. Obesity increases the risk of many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease, and can even reduce one's lifespan. Similarly, the prevalence of type 2 diabetes follows a comparable trend. As a result, researchers are striving to find solutions to reduce obesity rates, with a particular focus on gut health, which has been previously linked to both obesity and type 2 diabetes. Recent studies suggest that Akkermansia muciniphila (Akk) may have a positive probiotic effect on preventing the onset of type 2 diabetes and obesity. METHODS: We conducted a quantitative meta-analysis of 15 qualified animal studies investigating the effects of Akk administration as a probiotic. RESULTS: The statistical analyses showed that Akk administration significantly reduced body weight gain by 10.4% and fasting blood glucose by 21.2%, while also significantly improving glucose tolerance by 22.1% and increasing blood insulin levels by 26.9%. However, our analysis revealed substantial heterogeneity between the control and experimental groups across all subgroups. CONCLUSIONS: Overall, Akk appears to be effective at reducing the onset of type 2 diabetes and diet-induced obesity. Long-term studies with larger sample sizes are needed to confirm these beneficial effects, as the current animal studies were of short duration (less than 20 weeks).

Inulins, galacto-oligosaccharides (GOS) and polyphenols are considered to stimulate the growth of Akkermansia muciniphila (A. muciniphila) in the gut. We performed a meta-analysis of six microbiome studies (821 stool samples from 451 participants) to assess the effects of inulin, GOS, and polyphenols on the abundance of A. muciniphila in the gut. The intervention of GOS increased the relative abundance of A. muciniphila in healthy participants. Additionally, metabolic pathways associated with carbohydrate metabolism and short-chain fatty acid release were enriched following the GOS intervention. Furthermore, after the GOS intervention, the coexisting microbial communities of A. muciniphila, such as Eubacterium hallii and Bacteroides, exhibited an enhanced correlation with A. muciniphila. In conclusion, our findings suggest that GOS may promote the growth of A. muciniphila in the gut by modulating the gut microbiota composition.

Atherosclerosis is a major cause of death and disability. The beneficial effects of phytochemicals and probiotics on atherosclerosis have gained significant interest since these functional foods can improve inflammation, oxidative stress, and microbiome dysbiosis. The direct effect of the microbiome in atherosclerosis, however, needs further elucidation. The objective of this work was to investigate the effects of polyphenols, alkaloids, and probiotics on atherosclerosis using a meta-analysis of studies with mouse models of atherosclerosis. Identification of eligible studies was conducted through searches on PubMed, Embase, Web of Science, and Science Direct until November 2022. The results showed that phytochemicals reduced atherosclerosis, which was significant in male mice, but not in females. Probiotics, on the other hand, showed significant reductions in plaque in both sexes. Berries and phytochemicals modulated gut microbial composition by reducing the Firmicutes/Bacteroidetes (F/B) ratio and by upregulating health-promoting bacteria, including Akkermansia muciniphila. This analysis suggests that phytochemicals and probiotics can reduce atherosclerosis in animal models, with a potentially greater effect on male animals. Thus, consumption of functional foods rich in phytochemicals as well as probiotics are viable interventions to improve gut health and reduce plaque burden in patients suffering from cardiovascular disease (CVD).

INTRODUCTION: Cancer-related pain remains a critical clinical challenge, with existing opioid-based therapies often yielding inadequate relief and significant side effects. This study investigates the therapeutic potential of JK5G postbiotics-a formulation of inactivated Lactobacillus strains and metabolites-in modulating the gut-microbiome-immune axis to alleviate pain in cancer patients. METHODS: This study employs a randomized, double-blind, placebo-controlled trial design involving 149 participants divided into two groups: a control group receiving patient-controlled subcutaneous analgesia (PCSA) plus placebo, and an experimental group receiving PCSA plus JK5G postbiotics. The primary outcomes were changes in gut microbiota composition assessed by 16S rRNA gene sequencing, and quality of life (QoL). The secondary outcomes included fecal metabolomics, adverse effects (AEs), blood inflammatory cytokines, and lymphocyte subsets. This study was registered at www.chictr.org.cn(ChiCTR2500108811). RESULTS: JK5G supplementation significantly improved pain scores, QoL, and cognitive and social functioning compared to controls. Microbiome analysis revealed enrichment of beneficial taxa such as Akkermansia muciniphila and Bifidobacterium, alongside suppression of pathogenic Escherichia-Shigella. Machine learning identified five core microbial biomarkers (Akkermansia muciniphila, Bifidobacterium, Escherichia-Shigella, Blautia, Streptococcus), with SHAP analysis highlighting Akkermansia muciniphila and Bifidobacterium as top contributors. Metabolomic profiling demonstrated upregulation of 236 metabolites, including kynurenic acid and butyric acid, with tryptophan and butyrate metabolism emerging as key altered pathways. Immune profiling showed elevated CD3+CD4+ T cells and reduced TNF-α levels, while MIMOSA2 analysis linked microbial taxa to metabolic shifts, such as correlations between Ruminococcus torques and butyric acid. CONCLUSION: These findings suggest that JK5G may contribute to the amelioration of cancer-related pain by reshaping gut microbiota, modulating host metabolism, and enhancing immune responses. This study highlights the potential of JK5G postbiotics a

OBJECTIVE: Several factors, as genetics, diet, and gut microbiota, are associated with the development of type 1 diabetes (T1D). Akkermansia muciniphila, an abundant bacterium in human microbiota, has anti-inflammatory properties and can correct metabolic disorders. The effects of the administration of inulin, a prebiotic which increases Akkermansia muciniphila gut levels, are unknown in subjects with T1D. MATERIALS AND METHODS: 49 subjects with T1D, age 46 [37-53] years, 30 females (61%), duration of disease 20 [11-27] years, HbA1c 64 [59-72] mmol/mol, were randomized in group A (inulin 3 g twice daily for 3 months + insulin, n=24) and in group B (insulin alone, n=25). Body weight, glycated hemoglobin (HbA1c), daily insulin units, continuous glucose monitoring (CGM) metrics, and Bristol stool scale (BSS) score were collected at enrollment and after 3 months. RESULTS: After 3 months, subjects in group A showed a significant decrease in body weight [group A -2 (-3; 0) kg and group B 0 (-1; 1) kg, p=0.03] and daily insulin units [group A -1.5 UI (-3.1; 0) vs. group B 0.6 (0; 1.7), p=0.01]. After 3 months, changes in HbA1c and CGM were similar between groups. In both groups, there was no change in BSS score (p=0.39) nor in Akkermansia muciniphila gut levels. CONCLUSIONS: Inulin was associated with a slight body weight decrease and insulin need reduction, but not with an increase in Akkermansia muciniphila levels. More studies are required to explore this issue.

The relationship between frailty and gut microbiota has not been previously addressed in patients with cirrhosis. We studied by metagenomic shotgun sequencing the faecal microbiota composition associated with frailty in 29 patients with cirrhosis from a previous study (Román, Hepatol Commun 2024). Frail and prefrail patients were randomised to a multifactorial intervention (home exercise, branched-chain amino acids and a multistrain probiotic) or control for 12 months. We observed a positive correlation between the abundance of Rothia dentocariosa and the Liver frailty index (LFI), and between Bacteroides faecis and gait speed. After the multifactorial intervention, LFI improved and the main changes in the microbiota composition were a decrease in the abundance of Akkermansia muciniphila, and an increase in Streptococcus thermophilus, Lactobacillus acidophilus and several species of Bifidobacterium. We conclude that frailty in patients with cirrhosis was associated with a distinct microbiome signature. After a long-term multifactorial intervention, frailty improved in parallel with changes in microbiome composition. Trial Registration: ClinicalTrials.gov identifier: NCT04243148. © 2025 The Author(s). Liver International published by John Wiley & Sons Ltd.

AIM: Evidence suggests that the gut microbiome is involved in type 2 diabetes mellitus (T2DM). This study investigates the association between gut microbiota composition, cognitive function, and metabolic health in postmenopausal women with T2DM following a 12-week home-based multi-task exercise intervention. METHODS: Seventy postmenopausal women with T2DM were randomly assigned to either an intervention group, which performed home-based multi-task exercises, or a control group. Gut microbiota, cognitive function, physical fitness, and metabolic indices were assessed before and after the intervention. RESULTS: Exercise training significantly increased Akkermansia muciniphila and Faecalibacterium levels, and reduced Lactobacillus abundance (p < 0.05). Participants showed improvements in HDL levels, cognitive function, and physical fitness (p < 0.05). Among the microbial changes, an increased abundance of Akkermansia was significantly correlated with improvements in high-density lipoprotein (HDL) levels (r = 0.41) and cognitive function (r = 0.49). CONCLUSION: This study supports the potential effectiveness of multi-task exercise programs in enhancing physical fitness and metabolic health in postmenopausal women with T2DM. The findings also suggest a possible connection between the gut and the brain, with Akkermansia muciniphila emerging as a potential mediator. Investigating the Akkermansia-to-brain pathway represents a promising and emerging area of research that warrants further exploration.

Background/Objectives: An increasing number of apparently healthy individuals are adhering to a gluten-free lifestyle without any underlying medical indications, although the evidence for the health benefits in these individuals remains unclear. Although it has already been shown that a low- or gluten-free diet alters the gut microbiota, few studies have examined the effects of this diet on healthy subjects. Therefore, our aim was to evaluate whether and how a prolonged low-gluten diet impacts gut microbiota composition and function in healthy adults, bearing in mind its intimate link to the host's health. Methods: Forty healthy volunteers habitually consuming a gluten-containing diet (HGD, high-gluten diet) were included in a randomised control trial consisting of two successive 8-week dietary intervention periods on a low-gluten diet (LGD). After each 8-week period, gut microbiota composition was assessed by 16S rRNA gene sequencing, molecular quantification by qPCR, and a cultural approach, while its metabolic capacity was evaluated through measuring faecal fermentative metabolites by 1H NMR. Results: A prolonged period of LGD for 16 weeks reduced gut microbiota richness and decreased the relative abundance of bacterial species with previously reported potential health benefits such as Akkermansia muciniphila and Bifidobacterium sp. A decrease in certain plant cell wall polysaccharide-degrading species was also observed. While there was no major modification affecting the main short-chain fatty acid profiles, the concentration of the intermediate metabolite, ethanol, was increased in faecal samples. Conclusions: A 16-week LGD significantly altered both composition and metabolic production of the gut microbiota in healthy individuals, towards a more dysbiotic profile previously linked to adverse effects on the host's health. Therefore, the evaluation of longer-term LDG would consolidate these results and enable a more in-depth examination of its impact on the host's physiology, immunity, and metabolism.

Constipation is a prevalent symptom in adults and has been linked to an increased risk of serious complications, including cardiovascular and renal diseases. This study evaluated the effect of apple polyphenols on defecation among Japanese adults with a body mass index of ≥25 kg/m2 and <30 kg/m2 experiencing constipation who were otherwise healthy. After screening for eligibility, 24 participants were randomly assigned to either the Apple polyphenol or Placebo group in equal numbers. Participants consumed four tablets/day of either unripe apple-derived polyphenols (600 mg/day) or a placebo after breakfast with water for 12 wk. The primary outcome was weekly defecation frequency. Secondary outcomes included the number of days with defecation, the volume and feeling of defecation, the shape and smell of stools, fecal Akkermansia muciniphila counts, physical measurements, body composition, and blood lipid profile. The analysis included 12 participants in the Apple polyphenol and 11 in the Placebo group. After the 12-week intervention, the Apple polyphenol group had a significantly higher weekly defecation frequency versus the Placebo group (7.0 ± 2.1 vs. 4.9 ± 1.4 times; group difference: 2.2 times [95% CI 0.8-3.6], p = 0.004). No significant inter-group differences were observed in fecal A. muciniphila counts, physical measurements, body composition. While blood triglyceride levels tended to be lower in the Apple polyphenol group. These findings suggest that the consumption of polyphenols derived from immature apples may increase defecation frequency and ameliorate constipation; however, it appears not to affect A. muciniphila. Clinical trial registry: UMIN000050393.

OBJECTIVE: The objective of this study was to compare the impact of daily consumption of Akkermansia muciniphila postbiotic-fortified yogurt (AMY) with Lactobacillus rhamnosus postbiotic-fortified yogurt (LRY) on the health parameters in overweight and obese patients. METHODES: In this 8-week randomized double-blinded clinical trial, 66 people with overweight and obesity were randomly allocated to three groups: 1) AMY group (n = 22), 2) LRY group (n = 22), and 3) low-fat yogurt (LFY) as placebo (n = 22). The anthropometrics measurements, fasting blood glucose, lipid profile, liver enzymes, inflammatory and antioxidants biomarkers, appetite and mood status, physical activity and dietary intakes were measured at the beginning and end of the study. The registration number was IRCT20230522058257N1. RESULTS: In the AMY group, significant reductions were observed in waist circumference (P = 0.003), waist-to-height ratio (P = 0.004), body fat percentage (P = 0.032), aspartate aminotransferase levels (P = 0.045), and appetite scores (P = 0.047) compared with the control group. However, the results indicated that Lactobacillus rhamnosus-fortified yogurt did not demonstrate any beneficial impact on the health parameters. CONCLUSION: Our findings suggest that a dairy product enriched with Akkermansia muciniphila postbiotic may have favorable effects on weight management and liver enzyme levels in overweight and obese individuals; however, further studies are needed to confirm these results and explore underlying mechanisms.

BACKGROUND: Many patients with biochemically recurrent prostate cancer (BCRPC) prefer to delay androgen deprivation therapy (ADT) due to its adverse effects, highlighting the need for better-tolerated, effective alternatives. A subgroup analysis of our prior Phase II trial showed that muscadine grape skin extract (MPX) increased PSA doubling time (PSADT) in patients with SOD2 Ala/Ala variant which provided the rationale for this trial. METHODS: This randomized, double-blind, placebo-controlled trial, conducted at 14 sites, evaluated patients with BCRPC and SOD2 Ala/Ala genotype. Patients received 4000 mg MPX or placebo daily. The primary endpoint was on-study PSA slope with comparisons between treatment arms. Secondary endpoints were PSADT, PSA response (≥ 50% decrease), and PSA progression free survival (PFS). Correlative studies included markers of oxidative stress and gastrointestinal microbiota composition. RESULTS: At interim analysis, fifty-nine patients were randomized (MPX, n = 29; placebo, n = 30). On-study PSA slopes at 12, 24, 36, and 48 weeks showed no significant differences between the MPX and placebo arms (p = 0.49). The study was stopped due to futility. No significant differences were observed in PSADT, PSA response, median PSA PFS, or oxidative stress biomarkers. MPX was well-tolerated, with no grade 3-4 AEs attributable to the study drug. Microbiome analysis showed no significant differences in alpha diversity but revealed increased relative abundance of Roseburia faecis and Akkermansia muciniphila in the MPX group. CONCLUSIONS: Although MPX supplementation had no significant effect on PSA slope in men with BCRPC and SOD2 Ala/Ala variant, this study provides a rigorous evaluation of a natural product and highlights the importance of well-designed clinical trials in advancing evidence-based integrative oncology. TRIAL REGISTRATION: ClinicalTrials. gov, NCT03535675. © 2025 Wiley Periodicals LLC.

Major depression (MD) significantly impacts individual well-being and society. The vagus nerve plays a pivotal role in the gut-brain axis, facilitating bidirectional communication between these systems. Recent meta-analyses suggest potential antidepressant effects of probiotics, although their mechanisms remain unclear. This study aimed to assess the impact of a multi-species probiotic (OMNi-BiOTiC® STRESS Repair) on vagus nerve function in 43 MD patients and 43 healthy controls (HC). Participants received either probiotics or placebo twice daily. Serum and stool samples were collected at baseline, 7 days, 28 days, and 3 months. Vagus nerve (VN) function was evaluated using 24-hour electrocardiography (ECG) for heart rate variability (HRV), alongside stool microbiome analysis via 16S rRNA sequencing. After 3 months, MD patients receiving probiotics demonstrated significantly improved morning VN function compared to HC. MD participants who were in the probiotic group showed a significant increase in Christensellales, particularly Akkermansia muciniphila along with improved sleep parameters (use of sleep medication, sleep latency) as measured by the Pittsburgh Sleep Quality Inventory (PSI). This study highlights potential physiological benefits of probiotics in MD, potentially mediated through VN stimulation. Understanding these mechanisms could lead to novel therapeutic approaches for MD management.

BACKGROUND/OBJECTIVES: This study aimed to determine the impact of the daily consumption of kefir on the gut microbiome, body composition, and athletic performance of professional female soccer players. METHODS: The participants encompassed 21 females aged 18-29 years who were assigned to one of the two groups: the experimental group, which comprised females who consumed 200 mL of kefir daily for 28 days, and the control group, which comprised females who continued with their normal diet. Anthropometric measurements, dietary intake, the composition of the gut microbiome through 16S rRNA gene sequencing, and an athletic performance test known as the 30-15 Intermittent Fitness Test were performed before and after the intervention. RESULTS: The results of this study revealed that the consumption of kefir increased the microbial diversity (Shannon and Chao1 indices), wherein a significant increase was noted in the abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii, microorganisms that regulate energy metabolism and have anti-inflammatory effects. Furthermore, the athletic performance variables, including VO2max (mL.kg-1.min-1) and finishing speed (km/h), were strongly related to the abundance of these short-chain fatty acid-producing bacteria. A link between the microbiota profile and the dietary intake of fiber and protein as well as the body composition measurements was also established. CONCLUSIONS: This study indicated that kefir consumption can positively affect the gut microbiota, which could in turn affect the athletes' performance. Therefore, to determine the effects of kefir as a functional food in sports nutrition over a longer period, more research should be conducted.

BACKGROUND: The Capecitabine plus Oxaliplatin (XELOX) regimen is a first-line chemotherapy for colorectal cancer (CRC), but drug resistance remains a major therapeutic challenge. Our clinical observations suggest a positive correlation between fecal Akkermansia muciniphila bundance and chemotherapy responsiveness. Huang-Lian-Jie-Du Decoction (HLJDD), a traditional Chinese medicine with gut microbiota-modulating properties, may serve as a chemosensitizer, though its mechanisms are unclear. PURPOSE: This study aimed to evaluate whether HLJDD enhances XELOX efficacy in CRC and to elucidate the role of gut microbiota, particularly A. muciniphila, in this synergistic effect. METHODS: CRC patients receiving XELOX were analyzed for fecal A. muciniphila levels and treatment response. In MC38 and CT26 tumor-bearing mice, HLJDD was administered alone or combined with XELOX. Gut microbiota composition (16S rRNA sequencing), serum metabolites (untargeted metabolomics), and tumor immune infiltration (immunohistochemistry) were assessed. Co-housing experiments and direct A. muciniphila supplementation were conducted to validate microbiota-mediated mechanisms. RESULTS: Higher baseline A. muciniphila abundance correlated with improved XELOX response in CRC patients. HLJDD selectively promoted A. muciniphila proliferation in vitro and in vivo. In murine models, HLJDD synergized with XELOX, significantly suppressing tumor growth vs. XELOX alone. Multi-omics analyses revealed HLJDD-driven enrichment of tryptophan metabolism and increased 5-hydroxytryptophan levels, accompanied by enhanced CD8+ T cell infiltration and interferon-γ upregulation in tumors. Cohousing with HLJDD-treated mice or direct A. muciniphila gavage recapitulated the chemosensitizing effects, confirming gut microbiota's pivotal role. CONCLUSION: This study unveils a novel and multi-faceted therapeutic strategy: HLJDD overcomes XELOX resistance by specifically remodeling gut microbiota to expand A. muciniphila, which subsequently activates tryptophan metabolism and anti-tumor immunity. Our findings provide robust preclinical evidence for combining HLJDD with XELOX as a promising innovative approach to overcome CR

Recently, intestinal flora plays a vital role in the occurrence and development of tumors and there is link between cancer immunotherapy and Akkermansia muciniphila (Akk). However, the therapeutic efficacy of Akk in lung cancer remained unclear. Hence, our study is aimed at investigating the antitumor effects of cisplatin (CDDP) combined with Akk on lung cancer. Using the murine lung cancer model by subcutaneously inoculating Lewis lung cancer model, 50 mice were divided into five groups: normal, model, CDDP, CDDP+Akk, and CDDP+antibiotics. After treatment within 5 weeks, compared with the model group, the administered group improved the changes of tumor pathomorphology. Compared with the CDDP group, CDDP combining with Akk slowed down the growth of tumor volume, downregulated the levels of ki-67, p53, and factor-associated suicide (Fas) ligand proteins and upregulated Fas proteins, increased the levels of interferon-γ, interleukin-6, and tumor necrosis factor-α, and suppressed the expression of CD4+CD25+Foxp3+ Treg in mouse peripheral blood and spleen. In addition, transcriptome analysis indicated that Akk combining with CDDP increased obviously the levels of IFI27l2 and IGFBP7 and was related to those pathways including the cytokine-cytokine receptor interaction, Th17 cell differentiation, FOXO, JAK-STAT, and PI3K-Akt signaling pathways. These results suggested that the therapeutic efficacy of the combined treatment of Akk and CDDP was superior to the only CDDP treatment, which could enhance immune regulation and would be a promising strategy for the treatment of lung cancer.

BACKGROUND/OBJECTIVES: Sarcopenia, a condition marked by muscle wasting due to aging or inactivity, severely affects older populations. We previously showed that pasteurized Akkermansia muciniphila HB05 (HB05P), sourced from the breast milk of healthy Korean women, could mitigate muscle wasting in a dexamethasone-induced rat model. Here, we explored whether the oral administration of HB05P can enhance muscle strength and functionality in elderly individuals. Our objective was to determine if HB05P supplementation could benefit muscle performance in aging adults. METHODS: We conducted a 12-week, double-blind, placebo-controlled clinical trial involving 100 individuals aged 60 and above, randomly assigned to receive either HB05P (1.0 × 1010 cells/day) or a placebo. RESULTS: The HB05P group showed significant improvements in peak torque and peak torque per body weight of the left leg extensor muscles compared to the placebo group (p = 0.0103 and p = 0.0052). Furthermore, HB05P notably elevated follistatin levels, which counteract myostatin, relative to the placebo group (p = 0.0063). No notable safety concerns arose between the groups. CONCLUSIONS: HB05P is a promising postbiotic derived from Akkermansia muciniphila that may enhance muscle strength and be used as a safe postbiotic ingredient of Akkermansia muciniphila to improve muscle health.

The gut microbiota (GM) is a complex microbial ecosystem, and its alteration contributes to the development of several diseases including multiple sclerosis (MS). Progressive research concerning neurodegenerative diseases and GM reveals that GM dysbiosis has been linked to fostering the development and progression of MS. Among existing bacteria, F.prausnitzii and A.muciniphila are key species implicated in this disease. Thus, the present study systematically reviewed and synthesized the research on the involvement of F. prausnitzii and A. muciniphila in MS patients versus healthy individuals. We systematically searched PubMed, MEDLINE, EMBASE, and Web of Science databases for relevant published articles from January 2010 till January 2023. Out of 400 articles, 16 met the required criteria. The included research investigations originated from the US, Germany, Norway, Egypt, Iran, Brazil, China, the UK, and Romania. Most publications reported decreased levels of F. prausnitzii and increased levels of A. muciniphila in MS patients compared to controls. This review underscored the importance of the F. prausnitzii and A. muciniphila in MS, which could explain the chronic inflammation that characterizes this disease and not only help in understanding its etiology and progression but also open new avenues for the treatment strategies focusing on gut health. Moreover, understanding the role of F. prausnitzii and A. muciniphila could lead to novel biomarkers for early detection and progression monitoring MS. © 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

AIMS: The Mediterranean diet (MedD) is associated with improved metabolic health and modulation of gut microbiota (GM), both relevant to preventing type 2 diabetes (T2D) and cardiovascular disease (CVD). This systematic review and meta-analysis evaluated the effects of MedD-based dietary interventions on metabolic outcomes and GM composition in individuals at increased risk of T2D and CVD. DATA SYNTHESIS: We searched PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus up to October 11, 2024, for randomized controlled trials (RCTs) comparing MedD-based diets to control diets in adults. Studies reporting outcomes on glucose metabolism and GM composition were included. Random-effects meta-analyses were conducted on metabolic outcomes. GM findings were synthesized descriptively due to heterogeneity in sequencing methods and taxonomic reporting. Nine RCTs (n = 1337 participants) met the inclusion criteria. Compared with control diets, MedD interventions significantly reduced glycated hemoglobin (HbA1c) (mean difference -0.18, 95 % CI = -0.35, -0.01), LDL cholesterol (-0.10, 95 % CI = -0.19, -0.00), and triglycerides -0.20, 95 % CI = -0.28, -0.12). No significant effects were observed on fasting glucose, insulin, HOMA-IR, total cholesterol, or HDL cholesterol. A qualitative GM analysis showed increased α-diversity and enrichment of health-related taxa, including Akkermansia muciniphila and Roseburia spp. CONCLUSIONS: Our findings suggest that MedD interventions improve HbA1c, LDL cholesterol, and triglycerides, and promote beneficial GM changes. These may contribute to the metabolic benefits of the MedD. Future research should focus on individualized approaches, longer intervention periods, and mechanistic insights using multi-omics data to better understand the diet-microbiota-host interaction. PROTOCOL REGISTRATION: PROSPERO as CRD42023428016.

35. Nutr Metab Cardiovasc Dis. 2026 May;36(5):104433. doi: 10.1016/j.numecd.2025.104433. Epub 2025 Nov 3. Mediterranean diet, gut microbiota, and type 2 diabetes: A systematic review and meta-analysis of intervention trials. Lauria F(1), Formisano A(1), Dello Russo M(1), Quaglia C(2), Giacco R(1

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects nearly one-third of the adult population worldwide, and currently, there are no approved pharmacological therapies. Akkermansia muciniphila, a bacterium found in the gut, has been identified as a promising therapeutic candidate due to its influence on the gut-liver axis. OBJECTIVE: This systematic review aims to evaluate the efficacy of A. muciniphila in preclinical mouse models of NAFLD, focusing on its effects on body weight, glucolipid metabolism, liver function, gut barrier integrity, gut microbiota composition, inflammation, and immune response. METHODS: Following PRISMA 2020 guidelines, a comprehensive search was conducted in PubMed, Scopus, Web of Science, and Google Scholar until September 30, 2025, for studies investigating A. muciniphila interventions in NAFLD mouse models. Inclusion criteria comprised mouse models of NAFLD, MAFLD, or NASH that involved A. muciniphila administration alongside a control group. Data were extracted concerning study characteristics, intervention details, and outcomes. The quality assessment of the studies was performed using the SYRCLE's Risk of Bias tool. RESULTS: Thirteen studies were included, predominantly employing C57BL/6 mice and high-fat diets. Results indicated that A. muciniphila reduced body weight, hepatic steatosis, and serum lipid levels, while improving insulin sensitivity and decreasing liver enzyme levels (ALT, AST). It also enhanced gut barrier function by upregulating tight junction protein expression and reducing lipopolysaccharide (LPS) translocation. Furthermore, anti-inflammatory effects were evidenced by decreased levels of TNF-α, IL-6, and MCP-1, alongside immunomodulation through the balance of Th17 and Treg cells. CONCLUSION: A. muciniphila exhibits potential in the management of preclinical NAFLD by improving metabolic, hepatic, and gut-related parameters. However, the absence of clinical trials limits the translatability of these findings. Future clinical investigations are imperative to establish efficacy, optimize dosing, and evaluate long-term safety. TRIAL REGISTRATION: This systematic review has been documented with PROSPERO und

The gut-brain axis has emerged as a critical pathway influencing central nervous system (CNS) tumor biology through complex microbiome-mediated mechanisms. Understanding these interactions is essential for developing novel therapeutic strategies and biomarkers for CNS tumors. To systematically review and meta-analyze current evidence on gut microbiota interactions with CNS tumors, examining mechanisms, clinical correlations, therapeutic implications, and biomarker potential. We conducted a comprehensive systematic review following PRISMA guidelines, searching PubMed, EMBASE, Google Scholar, and Cochrane Library databases for studies published from 2010-2025. A random-effects meta-analysis of reported statistical outcomes was performed to quantify microbiome alterations using standardized mean differences (Cohen's d) and diagnostic accuracy measures. Analyses were based on published summary statistics rather than reprocessed raw sequencing data, acknowledging cross-study heterogeneity. From 161 identified records, 12 studies met inclusion criteria (6 clinical studies, n = 387 participants; 6 preclinical studies). Meta-analysis revealed significant Shannon diversity reduction in CNS tumor patients (Cohen's d = -1.237 [95% CI: -1.614, -0.860; 95% PI: -2.48, -0.12]) with moderate heterogeneity (I2 = 60.5%). Evidence demonstrated significant gut microbiome alterations with reduced microbial diversity, increased pathogenic bacteria (Akkermansia muciniphila: 2.23-fold increase, Fusobacterium spp.: 2.04-fold increase), and decreased beneficial bacteria (Bifidobacterium spp.: 47% reduction, Lachnospira spp.: 56% reduction). Diagnostic performance showed fair discrimination (pooled AUC = 0.786 [95% CI: 0.781, 0.791]). Key mechanisms include bidirectional tumor-microbiota interactions through immune system modulation, metabolic pathway alterations involving short-chain fatty acids, and inflammatory response modifications within the altered CNS immune privilege environment. Preliminary evidence suggests gut microbiota alterations in CNS tumor patients, but findings require validation in large, standardized cohorts before clinical application. Current evidence quality is low

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Emerging evidence highlights the gut microbiota, particularly Akkermansia muciniphila, as a key modulator in CRC pathogenesis. While often regarded as a beneficial commensal, its role in CRC appears complex and potentially dualistic. OBJECTIVE: This systematic review aims to comprehensively analyze the context-dependent role of A. muciniphila in CRC, evaluating its potential as a pathobiont. METHODS: We systematically reviewed human, animal, in vitro, and ex vivo studies on associations between A. muciniphila and CRC risk or outcomes. Database searches identified 34 eligible studies. Study quality was assessed using the GRADE criteria. RESULTS: From 244 initial records, 34 studies met the inclusion criteria. Findings reveal a stark dichotomy: non-viable forms of A. muciniphila-including pasteurized bacteria, outer membrane vesicles (OMVs), and purified proteins (e.g., Amuc_1100, Amuc_2172, Amuc_1434*)-consistently demonstrate anti-tumorigenic effects. These components enhance anti-tumor immunity by activating CD8 + T cells, promoting M1-like macrophage polarization via TLR2/NLRP3 signaling, and sensitizing tumors to chemotherapy and anti-PD-1 immunotherapy. Conversely, administration of live A. muciniphila can exert pro-tumorigenic effects, particularly in inflammatory contexts (e.g., colitis-associated CRC) or post-antibiotic settings, likely due to excessive mucin degradation and gut barrier disruption. Host factors such as obesity, sex, genetics, and microbial interactions further modulate its impact. CONCLUSION: A. muciniphila functions as a pathobiont in CRC, with its role critically dependent on its biological state and host context. Therapeutic strategies should shift from live probiotics to targeted postbiotic applications of its beneficial components to maximize efficacy and safety. © 2025. The Author(s).

Background: Depression and other stress-related mental disorders are the leading causes of disability worldwide, making them a significant global health challenge. This systematic review aimed to determine the effects of psychobiotic microorganisms on mental health outcomes, with particular focus on their sources, metabolites, and therapeutic potential for depression. Methods: A systematic review following PRISMA guidelines was conducted using publications from 2020 to 2024 in Web of Science, Scopus, and PubMed databases. Inclusion criteria encompassed studies examining psychobiotics and their effects on mental health in humans and experimental animals. Risk of bias assessment was performed using the Cochrane Risk of Bias Tool (ROB 2). Results: Of 369 identified articles, 45 met inclusion criteria. The predominant psychobiotic strains belonged to Lactobacillus (45.5%) and Bifidobacterium (29%) genera. Strain sources included commercial preparations (24%), human-derived (16%), and food-derived (16%) strains. Psychobiotic bacterial strains produce neuromodulatory metabolites, such as short-chain fatty acids (SCFAs), neurotransmitters (e.g., GABA and serotonin), and indole derivatives that influence the gut-brain axis. Their mechanisms of action include neurotransmitter regulation (27.1%), modulation of the gut microbiota (27.1%), SCFA production (16.9%), and control of inflammatory responses (15.3%). Lactobacillus plantarum, Bifidobacterium breve, and Akkermansia muciniphila demonstrated particularly promising effects. Conclusions: Psychobiotics show significant potential as adjunctive and therapeutic agents in depressive disorders through modulation of the gut-brain axis.

INTRODUCTION: Cancer patient's survival has gradually improved due to immune checkpoint inhibitors (ICIs). Several studies showed a possible association between the intestinal microbiome and ICI efficacy. Strategies for modifying the composition of the gut microbiome encompass various dietary interventions, which may have distinct impacts on the outcomes of ICI-treated patients. In our systematic review, we explored how dietary habits correlate with therapeutic responses in cancer patients and cancer mouse models undergoing immunotherapy. METHODS: A systematic review was conducted using search terms: "cancer", "immunotherapy", "diet", and "microbiome", from Medline, Web of Science, Scopus, and Cochrane Library databases. The outcomes in the clinical studies were overall response rate (ORR), overall survival (OS), or progression-free survival (PFS) in human studies. In mouse studies, change in tumor size was the endpoint. The comparator attributions were questionnaire-based dietary interventions. RESULTS: Nineteen articles met the inclusion criteria and were included in the review (6 prospective cohort studies, 1 cross-sectional observational study, and 12 mouse studies). A consistent association was observed between high (vs. low) fiber consumption and improved therapeutic response with a pooled odds ratio of 5.79 when including all human prospective cohort studies. In mice, limited availability of methionine, cysteine, and low intake of leucine and glutamine was linked to reduced tumor progression. Combining ICIs with intermittent fasting or a fasting-mimicking diet significantly decreased tumor volume in mouse melanoma models. In humans, a higher relative abundance of short-chain fatty acid (SCFA) and lactic acid-producing bacteria-particularly Faecalibacterium prausnitzii and Akkermansia muciniphila-correlated with objective response rates (ORR). Similar microbiome alterations were observed in mouse models. Increased fiber intake enhanced ICI efficacy in mice by modulating the gut microbiome, primarily via elevated SCFA production-an effect also reflected in human studies. CONCLUSION: Intermittent fasting, high fiber, and low sugar consumption are significant