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

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Oct. 30, 2024

Language: 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, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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

Language: 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, Journal Year: 2025, Volume and Issue: unknown, P. 107693 - 107693

Published: March 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.

Language: Английский

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

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. jnnp - 335593

Published: April 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.

Language: Английский

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

JAMA Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

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Dipeptidyl peptidase-4 inhibitors enhance memory retention via neuropeptide Y

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177556 - 177556

Published: March 1, 2025

Language: Английский

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

Nutrients, Journal Year: 2025, Volume and Issue: 17(8), P. 1303 - 1303

Published: April 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.

Language: Английский

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Gut-brain axis as a bridge in obesity and depression: Mechanistic exploration and therapeutic prospects

World Journal of Psychiatry, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 18, 2024

A recent study by Wang et al, published in the World Journal of Psychiatry, provided preventative and therapeutic strategies for comorbidity obesity depression. The gut-brain axis, which acts as a two-way communication system between gastrointestinal tract central nervous system, plays pivotal role pathogenesis these conditions. Evidence suggests that metabolic byproducts, such short-chain fatty acids, lipopolysaccharide bile are generated gut microbiota, along with neurotransmitters inflammatory mediators within modulate host's processes, neuronal regulation, immune responses through diverse mechanisms. interaction depression via axis involves disruptions microbiota balance, responses, alterations neuroendocrine system. Modulating example, ketogenic diet, use probiotics, supplementation antioxidants, offers new remedial approaches Future research explores mechanisms is needed to provide more evidence clinical treatment.

Language: Английский

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Glucagon-like peptide-1 receptor agonists: Exploring the mechanisms from glycemic control to treatment of multisystemic diseases

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(36), P. 4036 - 4043

Published: Sept. 20, 2024

This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani, which examined therapeutic potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for metabolic dysfunction-associated fatty liver disease. We provide supplementary to their research, highlighting broader systemic implications GLP-1RAs, synthesizing current understanding mechanisms trajectory research in this field. GLP-1RAs are revolutionizing treatment type 2 diabetes mellitus beyond. Beyond glycemic control, demonstrate cardiovascular renal protective effects, offering managing diabetic kidney disease al-ongside renin–angiotensin–aldosterone system inhibitors. Their role bone metabolism hints benefits osteoporosis, while neuroprotective properties show promise Alzheimer's modulating neuronal insulin signaling. Additionally, they improve hormonal profiles polycystic ovary syndrome. highlights multifaceted emphasizing need ongoing fully realize across range multisystemic diseases.

Language: Английский

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Deficient Memory, Long-Term Potentiation and Hippocampal Synaptic Plasticity in Galectin-4-KO Mice.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract Intestinal infections trigger inflammation and can contribute to degenerative cognitive brain pathologies through the microbiota-gut-brain axis. Galectin-4 is an intestinal lectin key in control of pathogenic bacterial infections. Here we report that galectin-4 deficient mice (Lgals4-KO) show altered commensal microbiota absence pathogens, defining a new role modulation bacteria. Strikingly, Lgals4-KO present memory formation, impaired hippocampal long-term potentiation (LTP) vivo ex . Furthermore, neurons reduced activation AMPA receptor CaMKII upon chemically induced LTP vitro These also display significantly lower dendritic spine density shorter length dendrites, as well increased area postsynaptic densities, all coherent with alteration synaptic function. In all, our results demonstrate induces dysfunctions impairment, along changes gut microbial composition, suggesting variations endogenous may cause or such neurological pathologies.

Language: Английский

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