Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study

Han, Shuai; Gao, Jiapei; Wang, Zi; Xiao, Yinggang; Ge, Yali; Liang, Yongxin; Gao, Ju

doi:10.3389/fmicb.2024.1343763

Cited by 3 publications

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Gut Microbiota and DTI Microstructural Brain Alterations in Rodents Due to Morphine Self-Administration

Brunetti,

Zhou,

Shuchi

et al. 2024

Preprint

View full text Add to dashboard Cite

The opioid epidemic is an evolving health crisis in need of interventions that target all domains of maladaptive changes due to chronic use and abuse. Opioids are known for their effects on the opioid and dopaminergic systems, in addition to neurocircuitry changes that mediate changes in behavior; however, new research lines are looking at complementary changes in the brain and gut. The gut-brain axis (GBA) is a bidirectional signaling process that permits feedback between the brain and gut and is altered in subjects with opioid use disorders. In this work, we determine longitudinal, non-invasive, and in-vivo complementary changes in the brain and gut in rodents trained to self-administer morphine for two weeks using MRI and 16S rDNA analysis of fecal matter. We assess the changes occurring during both an acute phase (early in the self-administration process, after two days of self-administration) and a chronic phase (late in the self-administration process, after two weeks of self-administration), with all measurements benchmarked against baseline (naive, non-drug state). Rats were surgically implanted with an intravenous jugular catheter for self-administration of morphine. Rats were allowed to choose between an active lever, which delivers a single infusion of morphine (0.4 mg/kg/infusion), or an inactive lever, which had no consequence upon pressing. Animals were scanned in a 7T MRI scanner three times (baseline, acute, and chronic), and before scanning, fecal matter was collected from each rat. After the last scan session, a subset of animals was euthanized, and brains were preserved for immunohistochemistry analysis. We found early changes in gut microbiota diversity and specific abundance as early as the acute phase that persisted into the chronic phase. In MRI, we identified alterations in diffusivity indices both within subjects and between groups, showing a main effect in the striatum, thalamus, and somatosensory cortex. Finally, immunohistochemistry analyses revealed increased neuroinflammatory markers in the thalamus of rats exposed to morphine. Overall, we demonstrate that morphine self-administration shapes the brain and gut microbiota. In conclusion, gut changes precede the anatomical effects observed in MRI features, with neuroinflammation emerging as a crucial link mediating communication between the gut and the brain. This highlights neuroinflammation as a potential target in addressing the impacts of opioid use.

show abstract

Gut Microbiota and DTI Microstructural Brain Alterations in Rodents Due to Morphine Self-Administration

Brunetti,

Zhou,

Shuchi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Causal influence of immune factors on the risk of diabetic retinopathy: a mendelian randomization study

Li,

Xiang,

Mou

et al. 2024

Diabetol Metab Syndr

View full text Add to dashboard Cite

Objectives Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients. Various mechanisms have been implicated in the pathogenesis of DR. Previous studies have observed the relationship between immune factors and DR, but the causal relationship has not been determined. Methods We conducted a two-sample Mendelian randomization (MR) analysis of 731 immune cells and DR, using publicly available genome-wide association study (GWAS) summary statistics, to evaluate potential causal relationships between them. Four types of immune traits were included in the analysis through flow cytometry. GWAS statistics for DR were obtained from the Finngen database, which performed GWAS on 190,594 European individuals (Ncase = 14,584, Ncontrol = 176,010) to assess genetically predicted DR. The primary method used to perform causality analysis was inverse variance weighting (IVW). Results Following false discovery rate (FDR) correction, 11MFI-DR, 5AC-DR, 5RC-DR, and 1MP-DR reached a significant causal association level (P FDR < 0.05). Notably, all AC traits exhibited potential associations with a decreased risk of DR(OR < 1), while a majority of MFI traits, along with the singular MP trait, exhibited potential associations with an increased risk of DR (OR > 1). The highest proportion of T-cell subsets in the final results. Conclusion This study elucidates that the progression of DR is intricately influenced by immune responses, thereby confirming the immunological susceptibility of DR. Our findings may offer new targets for diagnosing and treating DR, as well as aid in developing therapeutic strategies from an immunological standpoint. Supplementary Information The online version contains supplementary material available at 10.1186/s13098-024-01441-6.

show abstract

The role relationship played by immune cells and circulating inflammatory proteins in NAFLD

Chi,

Zhang,

Bai

et al. 2024

Preprint

View full text Add to dashboard Cite

Objective The mechanisms by which immune cells and inflammatory factors influence Non-Alcoholic Fatty Liver Disease (NAFLD) remain unclear. This study employs Mendelian randomization (MR) to investigate the relationship between immune cells, inflammatory factors, and NAFLD, as well as the proportion of their mutual mediation effects on NAFLD. Methods This study utilizes MR analysis, examining the causal relationship between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and NAFLD. The data are sourced from publicly available data in the GWAS Catalog. The research process consists of two steps, analyzing them through the assessment of their mediating effects. To obtain reliable results, MR analysis necessitates the fulfillment of three fundamental assumptions. In the selection of instrumental variables, SNPs are screened, requiring significant associations with the exposure factors and no association with the outcomes. Statistical analyses employ methods such as IVW, WM, and MR-Egger to evaluate the causal relationship between exposure and outcomes. Sensitivity analyses are conducted, examining heterogeneity and horizontal pleiotropy. Results Ultimately, among the 731 immune cell phenotypes, 21 phenotypes are found to have a causal relationship with NAFLD, with 6 circulating inflammatory protein phenotypes playing intermediary roles. Among the 91 circulating inflammatory protein phenotypes, 7 inflammatory factor phenotypes are found to have a causal relationship with NAFLD, with 5 immune cell phenotypes playing intermediary roles. Conclusion Immune cells and circulating inflammatory proteins play a crucial role in NAFLD, and our study may provide new insights for the diagnosis and treatment of NAFLD in the future.

show abstract

Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study

Cited by 3 publications

References 51 publications

Gut Microbiota and DTI Microstructural Brain Alterations in Rodents Due to Morphine Self-Administration

Gut Microbiota and DTI Microstructural Brain Alterations in Rodents Due to Morphine Self-Administration

Causal influence of immune factors on the risk of diabetic retinopathy: a mendelian randomization study

The role relationship played by immune cells and circulating inflammatory proteins in NAFLD

Contact Info

Product

Resources

About