Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model

Background: Gut microbiota dysbiosis is associated with the development of non‑alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short‑chain fatty acid production. The aim of this study was to describe the impact of a choline‑deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH. Results: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short‑chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids. Conclusions: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH

Association between solar insolation and a history of suicide attempts in bipolar I disorder

In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p <0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.Peer reviewe

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p &lt; 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

Deciphering the association networks of mycobiome communities among the elderly Danes

Changes of microbial communities have been linked to frailty in elderly, yet the presence of fungal communities and their associations are little understood. This study attemps to identify biologically meaningful gut microbial fungal associations during aging. Faecal samples of 100 Danes of 65 years or older were collected, and sequenced by high-throughput tag-encoded sequencing of ITS2 gene fragments. The sequences were analysed using QIIME and CoNet to characterise fungal communities, and generate association networks, respectively. HbA1c, identified as the principal node, was grouped into 3 clusters based on glycated glucose levels. The clusters correspond to the phyla Ascomycota, Basidiomycota and Zygomycota, with the genera Penicillium, Candida, and Aspergillus being particularly abundant within each cluster. Interestingly, Bray-Curtis dissimilarity matrices showed significant (P<0.05) variation between clusters. These findings suggest that the presences of specific gut mycobiome members are associated with glycemic behaviours among the healthy individuals of the elderly Danish population

Deciphering the association networks of mycobiome communities among the elderly Danes

Changes of microbial communities have been linked to frailty in elderly, yet the presence of fungal communities and their associations are little understood. This study attemps to identify biologically meaningful gut microbial fungal associations during aging. Faecal samples of 100 Danes of 65 years or older were collected, and sequenced by high-throughput tag-encoded sequencing of ITS2 gene fragments. The sequences were analysed using QIIME and CoNet to characterise fungal communities, and generate association networks, respectively. HbA1c, identified as the principal node, was grouped into 3 clusters based on glycated glucose levels. The clusters correspond to the phyla Ascomycota, Basidiomycota and Zygomycota, with the genera Penicillium, Candida, and Aspergillus being particularly abundant within each cluster. Interestingly, Bray-Curtis dissimilarity matrices showed significant (P<0.05) variation between clusters. These findings suggest that the presences of specific gut mycobiome members are associated with glycemic behaviours among the healthy individuals of the elderly Danish population