Etiology, effects and management of comorbidities in multiple sclerosis: recent advances

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 30, 2023

Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that MS have an increased incidence of ischemic heart disease, cerebrovascular peripheral vascular and psychiatric disorders as compared to without MS. People from underrepresented minority immigrant groups higher comorbidity burdens. Comorbidities exert effects throughout the disease course, symptom onset through diagnosis end life. At individual level, is associated relapse rates, greater physical cognitive impairments, lower health-related quality life, mortality. level health system society, care utilization, costs work impairment. A nascent literature suggests affects outcomes comorbidities. Comorbidity management needs be integrated into care, this would facilitated by determining optimal models care.

Язык: Английский

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Multiple sclerosis and inflammatory bowel disease: A systematic review and meta‐analysis

Annals of Clinical and Translational Neurology, Год журнала: 2022, Номер 9(2), С. 132 - 140

Опубликована: Янв. 29, 2022

Abstract Background Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have established an association between MS IBD, including Crohn's (CD) ulcerative colitis (UC), but the results were inconsistent. The aim this study was to quantify prevalences IBD. Methods PubMed, Web Science, Embase databases searched through November 2020 for reporting data on among patients with IBD vice versa. main outcomes proportion in versa, as well (risk ratio [RR]) Results Based analysis 17 studies, prevalence 0.2% (95% CI 0.1–0.4%), while 0.6% 0.4–0.9%). Patients had a higher than controls (RR = 1.53, 95% 1.38–1.70, p < 0.00001). There similarly high risk developing CD 1.41, 1.14–1.74, 0.001) or UC 1.42, 1.17–1.71, 0.0003) ( subgroup differences: 0.97). 1.91, 1.06–3.45, 0.03). Conclusions Clinicians should be aware increased comorbidity during diagnostic process. Systematic diagnosis management at earlier stage suggested.

Язык: Английский

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Inflammatory Bowel Disease and Neurodegenerative Diseases

Gut and Liver, Год журнала: 2023, Номер 17(4), С. 495 - 504

Опубликована: Фев. 27, 2023

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci comorbidities IBD mood disorders.These new discoveries stem from improved understanding the gut-microbiome-brain axis: specifically, ability intestinal microbiota to modulate inflammation regulate neuromodulatory compounds.Clinical retrospective studies incorporating large sample sizes population-based cohorts have confirmed relevance chronic neurodegeneration in clinical medicine.In this review, we expound upon current knowledge on axis, highlighting several plausible mechanisms linking with neurodegeneration.We also summarize known associations Parkinson disease, Alzheimer vascular dementia ischemic stroke, multiple sclerosis a context.Finally, discuss implications axis preventing, diagnosing, managing among non-IBD patients.(

Язык: Английский

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Lack of Causal Associations of Inflammatory Bowel Disease with Parkinson's Disease and Other Neurodegenerative Disorders

Movement Disorders, Год журнала: 2023, Номер 38(6), С. 1082 - 1088

Опубликована: Март 23, 2023

Observational studies have indicated associations between inflammatory bowel disease (IBD) and neurodegenerative diseases, including Parkinson's (PD).To evaluate the causal of IBD with PD other selected disorders using updated data.Bidirectional two-sample Mendelian randomization genome-wide association summary statistics PD.We found a lack evidence for on (odds ratio [OR], 1.014; 95% confidence interval [CI], 0.967-1.063; P = 0.573). Reverse analysis also no effect (OR, 0.978; CI, 0.910-1.052; 0.549). The causality Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis was unfounded (all > 0.05).The analyses provide clear or three diseases. Potential confounders might contribute to previously observed associations, further investigations are warranted. © 2023 International Parkinson Movement Disorder Society.

Язык: Английский

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Systematic dissection of pleiotropic loci and critical regulons in excitatory neurons and microglia relevant to neuropsychiatric and ocular diseases

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 25, 2025

Advancements in single-cell multimodal techniques have greatly enhanced our understanding of disease-relevant loci identified through genome-wide association studies (GWASs). To investigate the biological connections between eye and brain, we integrated bulk multiomic profiles with GWAS summary statistics for eight neuropsychiatric five ocular diseases. Our analysis uncovered latent factors explaining 61.7% genetic variance across these 13 diseases, revealing diverse correlational patterns among them. We 45 pleiotropic 91 candidate genes that contribute to disease risk. By integrating profiles, implicated excitatory neurons microglia as key contributors eye-brain connections. Polygenic enrichment further 15 regulons 16 were linked comorbid conditions. Functionally, neuron-specific involved axon guidance synaptic activity, while microglia-specific associated immune response cell activation. In sum, findings underscore link psychiatric disorders

Язык: Английский

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Are neurodegenerative diseases associated with an increased risk of inflammatory bowel disease? A two-sample Mendelian randomization study

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Сен. 8, 2022

Background Several studies have shown that neurodegenerative diseases (e.g., Parkinson’s disease [PD] and Alzheimer’s [AD]) are associated with inflammatory bowel (IBD), but the causality direction of their associations remain unclear. Mendelian randomization (MR) explored causal effects IBD on PD AD. However, only a few examined this reverse association. Thus, study aimed to explore whether there genetically predicted AD IBD, using two-sample MR study. Methods Summary statistics for ulcerative colitis (UC), Crohn’s (CD) were derived from genome-wide association (GWAS) meta-analysis, which included International Genetics Consortium UK (n=59,957). Genetic variants largest meta-analysis GWAS (n=1,474,097) (n=455,258) used as instrumental variables. We multiple methods, including inverse variance weighted (IVW), median (WM), MR-Egger regression, mode, Robust Adjusted Profile Score (RAPS) estimate IBD. To confirm validity analysis, we also evaluated pleiotropic effects, heterogeneity, leave-one-out sensitivity analysis drive associations. Results The results IVW method, WM, RAPS showed was significantly an increased risk UC (odds ratio [ OR ] =1.068, WM =1.107, =1.069, all P &lt;0.05). Additionally, found significant CD ( =1.064, =1.065, &lt;0.05) =1.062, =1.063, method RAPS. no evidence in UC, or among methods. In analyses, horizontal pleiotropy (all &gt;0.05), statistical heterogeneity. effect estimations robust. Conclusions Our corroborated between did not support More animal experiments population-based observational required clarify underlying mechanisms

Язык: Английский

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Impact of Microbiome–Brain Communication on Neuroinflammation and Neurodegeneration

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14925 - 14925

Опубликована: Окт. 5, 2023

The gut microbiome plays a pivotal role in maintaining human health, with numerous studies demonstrating that alterations microbial compositions can significantly affect the development and progression of various immune-mediated diseases affecting both digestive tract central nervous system (CNS). This complex interplay between microbiota, gut, CNS is referred to as gut-brain axis. microbiota pathogenesis neurodegenerative has gained increasing attention recent years, evidence suggests dysbiosis may contribute disease progression. Clinical have shown composition multiple sclerosis patients, decrease beneficial bacteria an increase pro-inflammatory bacteria. Furthermore, changes within community been linked Parkinson's Alzheimer's disease. Microbiota-gut-brain communication impact through mechanisms, including regulation immune function, production metabolites, well modulation host-derived soluble factors. review describes current literature on axis highlights novel systems allow cross-talk host might influence neuroinflammation neurodegeneration.

Язык: Английский

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Genetic correlation, causal relationship, and shared loci between vitamin D and COVID‐19: A genome‐wide cross‐trait analysis

Journal of Medical Virology, Год журнала: 2023, Номер 95(5)

Опубликована: Май 1, 2023

Abstract Observational studies have shown that vitamin D supplementation reduces the risk of COVID‐19 infection, yet little is known about shared genomic architectures between them. Leveraging large‐scale genome‐wide association study (GWAS) summary statistics, we investigated genetic correlation and causal relationship genetically determined using linkage disequilibrium score regression Mendelian randomization (MR) analyses, conducted a cross‐trait GWAS meta‐analysis to identify overlapping susceptibility loci We observed significant predicted ( r g = −0.143, p 0.011), infection would decrease by 6% for every 0.76 nmol L −1 increase serum 25 hydroxyvitamin (25OHD) concentrations in generalized MR (OR 0.94, 95% CI: 0.89–0.99, 0.019). identified rs4971066 EFNA1 ) as locus joint phenotype COVID‐19. In conclusion, associated with Increased levels 25OHD concentration may benefit prevention treatment

Язык: Английский

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Anti-CD20 monoclonal antibody (mAb) therapy and colitis: A case series and review

Multiple Sclerosis and Related Disorders, Год журнала: 2023, Номер 75, С. 104763 - 104763

Опубликована: Май 15, 2023

Язык: Английский

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Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis

JHEP Reports, Год журнала: 2024, Номер 6(6), С. 101037 - 101037

Опубликована: Фев. 12, 2024

Background&Aims: Inflammatory bowel disease (IBD) is commonly associated with extraintestinal complications, including autoimmune liver disease. The co-occurrence of IBD and primary biliary cholangitis (PBC) has been increasingly observed, but the underlying relationship between two conditions remains unclear.MethodsUsing genome-wide association studies (GWAS) summary statistics, we investigated causal effect PBC IBD, Crohn's (CD) ulcerative colitis (UC). We also analyzed shared genetic architecture using data from GWAS, bulk tissue RNA sequencing, single-cell explored potential functional genes.ResultWe found a strong positive correlation (LDSC: rg =0.2249, P = 3.38 × 10-5). Cross-trait analysis yielded 10 risk SNPs, as well 9 novel that were both traits. Using Mendelian randomization, established stable on IBD. Genetically predicted was to have (1.105[95% confidence interval (CI): 1.058-1.15], 1.16 x 10−10) not vice versa. identified tissue-specific heritability enrichment for (including CD UC) in lung, spleen, whole blood samples. Furthermore, observed specific cell types (T cells, B NK cells) their subtypes. genes base SMR.ConclusionOur study detected demonstrated genetically These findings shed light biological basis comorbidity PBC, important implications intervention treatment targets these diseases simultaneously.

Язык: Английский

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