The interplay of gut microbiota, obesity, and depression: insights and interventions

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Окт. 30, 2024

Язык: Английский

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Effects of GLP-1 Analogues and Agonists on the Gut Microbiota: A Systematic Review

Nutrients, Год журнала: 2025, Номер 17(8), С. 1303 - 1303

Опубликована: Апрель 9, 2025

Background: GLP-1 analogues are a relatively new class of medications that form the cornerstone diabetes treatment. They possess invaluable glucose-lowering properties without hypoglycemic effects as well strong cardioprotective effects. The gut microbiome has become focus numerous studies, demonstrating its influence not only on but also overall well-being entire body. However, analogs microbiota remain uncertain. Scope review: Our systematic review (based PRISMA guidelines) aimed to gather knowledge analogue composition, richness, and abundance in both animal human models. Conclusions: Thirty-eight studies were included this review. have demonstrated notable impact diversity microbiota. We can conclude, following obtained research results our study, liraglutide promotes growth beneficial genera relevant for metabolic functions. Exenatide exendin-4 administration showed various composition studies. In models, it increased associated with improved metabolism; however, linked better functions escalated inflammation increased. Following dulaglutide administration, increases Bacteroides, Akkermansia, Ruminococcus, connected an model, significant. Finally, varied after semaglutide treatment, which A. muciniphila, known positive functions, increased; microbial decreased. Semaglutide treatment provided indicating many confounding factors semaglutide’s Results due dissimilarities studied populations duration Further is essential confirm these findings recognize their implications clinical outcomes patients.

Язык: Английский

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Association of GLP1R locus with mental ill‐health endophenotypes and cardiometabolic traits: A trans‐ancestry study in UK Biobank

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Aims Glucagon‐like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off‐target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill‐health (MIH) cardiometabolic phenotypes across diverse populations within UK Biobank. Materials Methods All variants minor allele frequency >1% were investigated associations MIH phenotypes. Linear or Logistic regression analyses (adjusted age, sex, population structure genotyping chip) conducted separately unrelated individuals of self‐reported white British ( N = 408 774), European 50 314), South Asian 7667), multiple‐ancestry groups 10 437) African‐Caribbean 7641) subsets. ancestries subsequently combined an inverse variance‐weighted fixed effects meta‐analysis. Bonferroni correction multiple testing was applied (for number independent variants). Results Associations identified between body mass index (BMI), blood pressure all ancestries. except had significant (mood instability: rs111265626‐G, odds ratio [OR] 0.851 [confidence interval, CI 0.79–0.92], risk‐taking behaviour: rs75408972‐T, OR 1.05 [CI 1.03–1.08] chronic pain: rs9296280‐C, 0.645 0.54–0.78]). The trans‐ancestry meta‐analysis showed mainly consistent effect sizes directions metabolic traits, but discordant associations. Only signals pain, stroke BMI influenced expression . Conclusions ancestries, are more varied. Any observed changes GLP1RA likely not acting directly through

Язык: Английский

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From Gut to Brain: The Role of Gut Dysbiosis, Bacterial Amyloids, and Metabolic Disease in Alzheimer’s Disease

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107693 - 107693

Опубликована: Март 1, 2025

Gut microbial dysbiosis, or altered gut communities, in Alzheimer's Disease suggests a pathogenic role for inflammation and products shaping neuroinflammatory environment. Similarly, metabolic diseases, such as obesity diabetes, are also associated with an increased risk of Disease. As the landscape shifts during inflammation, turn impacts processes, we explore how these interconnected pathways may contribute to progression Additionally, discuss bacterial amyloids produced by microbes, which exacerbate amyloid aggregation brain neurodegenerative processes. Furthermore, highlight potential therapeutic strategies aimed at reducing improving health, decreasing content means mitigate progression. These approaches, targeting gut-brain-metabolic axis, could offer promising avenues delaying preventing cognitive decline affected individuals.

Язык: Английский

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Suicide and Self-Harm Events With GLP-1 Receptor Agonists in Adults With Diabetes or Obesity

JAMA Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Importance Bariatric surgery, once the criterion standard in obesity treatment, has a small but concerning association with increased suicidality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat diabetes, now provide substantial efficacy treatment of obesity. However, concerns risk suicidality these medicines have been raised. Objective To evaluate and self-harm randomized, placebo-controlled trials GLP-1 RAs adults diabetes or Data Sources MEDLINE, Embase, ClinicalTrials.gov, Cochrane databases were systematically searched from inception August 29, 2023. Study Selection Reports randomized clinical (RCTs) lasting 6 more months comparing placebo for published peer-reviewed journals identified. Two independent reviewers screened all search-identified studies inclusion. Records outcomes queried primary papers, ClinicalTrials.gov entries, corresponding authors. Extraction Synthesis researchers abstracted data assessed quality validity using PRISMA guidelines. pooled random-effects models. Main Outcomes Measures Pooled incidence completed attempted suicide, occurrences suicidal ideation, self-harm. Results A total 27 144 RCTs meeting inclusion criteria recorded suicide and/or self-harm-related events included 32 357 individuals receiving 046 treated placebo, over 74 740 68 095 person-years follow-up, respectively. Event was very low RA (0.044 per 100 person-years) (0.040 groups, no statistically significant difference (rate ratio [RR], 0.76; 95% CI, 0.48-1.21; P = .24). Subgroup analyses did not suggest differences based on status used. Five considered at bias due loss than 5% participants follow-up. Otherwise, found be heterogeneous nor high bias. Conclusions Relevance There is unlikely an increase suicide-related adverse among within context RCTs. While findings may further ease about effects, continued monitoring warranted identify particular patients who as extended use expands.

Язык: Английский

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Dipeptidyl peptidase-4 inhibitors enhance memory retention via neuropeptide Y

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177556 - 177556

Опубликована: Март 1, 2025

Язык: Английский

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Glucagon-like peptide-1 receptor agonists for major neurocognitive disorders

Journal of Neurology Neurosurgery & Psychiatry, Год журнала: 2025, Номер unknown, С. jnnp - 335593

Опубликована: Апрель 10, 2025

Disease-modifying treatments for major neurocognitive disorders, including Alzheimer’s disease, Parkinson’s disease and other cognitive deficits, are among the main unmet needs in modern medicine. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently licensed treatment of type 2 diabetes mellitus obesity, offer a novel, multilayered mechanism intervention neurodegeneration through intermediate, aetiology-agnostic pathways, likely involving metabolic, inflammatory several relevant neurobiological processes. In vitro animal studies have revealed promising signals neuroprotection, with preliminary supportive evidence emerging from recent pharmacoepidemiological investigations clinical trials. this article, we comprehensively review that investigate impact GLP-1RAs on various aetiologies impairment dementia syndromes. Focusing human studies, highlight how brain energy homeostasis, neurogenesis, synaptic functioning, neuroinflammation cellular stress responses, pathological protein aggregates, proteostasis, cerebrovascular system blood-brain barrier dynamics may underlie GLP-1RA putative neuroprotective effects. We then report appraise observational investigations, trials pooled analyses. Finally, discuss current challenges perspectives ahead research implementation care people their individual penetrance potential, need response biomarkers stage-based indications, possible non-specific effects health, profile terms adverse events unwanted effects, lack long-term data efficacy safety, issues surrounding cost availability treatment.

Язык: Английский

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Insulin Resistance: The Role in Comorbid Type 2 Diabetes Mellitus and Depression

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер unknown, С. 106218 - 106218

Опубликована: Май 1, 2025

Язык: Английский

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Gut microbiota mediates semaglutide attenuation of diabetes-associated cognitive decline

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00615 - e00615

Опубликована: Май 1, 2025

Язык: Английский

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Bidirectional Interactions Between the Gut Microbiota and Incretin-Based Therapies

Life, Год журнала: 2025, Номер 15(6), С. 843 - 843

Опубликована: Май 23, 2025

Obesity, insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic syndrome have been largely correlated to a reduction in bacterial load diversity, resulting condition known as intestinal dysbiosis. The recent emergence of novel antidiabetic medications has demonstrated exert favourable influence on the composition microbiota. Incretin-based therapy exerts multifaceted gut microbiota, leading alterations flora. Of particular significance is capacity numerous metabolites produced by microbiota modulate activity hormonal secretion enteroendocrine cells. This review examines effects dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists GLP-1/gastric inhibitory polypeptide (GIP) dual both mice human subjects. nature this interaction complex bidirectional. present study demonstrates involvement incretinic axis modulating microbial composition, with objective providing preventative strategies potential personalised therapeutic targets for obesity T2DM.

Язык: Английский

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