Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures.

Neuropsychiatric diseases and obesity are major components of morbidity and health care costs, with genetic, lifestyle, and gut microbiome factors linked to their etiology. Dietary and weight-loss interventions can help improve mental health, but there is conflicting evidence regarding their efficacy; and moreover, there is substantial interindividual heterogeneity that needs to be understood. We aimed to identify genetic and gut microbiome factors that explain interindividual differences in mental health improvement after a dietary and lifestyle intervention for weight loss. We recruited 369 individuals participating in Digbi Health's personalized digital therapeutics care program and evaluated the association of 23 genetic scores, the abundance of 178 gut microbial genera, and 42 bacterial pathways with mental health. We studied the presence/absence of anxiety or depression, or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight. Participants lost on average 5.4% body weight and >95% reported improving mental health symptom intensity. There were statistically significant correlations between: (a) genetic scores with anxiety or depression at baseline, gut microbial functions with sleep problems at baseline, and (b) genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Our results are concordant with previous findings, including the association between anxiety or depression at baseline with genetic scores for alcohol use disorder and major depressive disorder. As well, our results uncovered new associations in line with previous epidemiological literature. As evident from previous literature, we also observed associations of gut microbial signatures with mental health including short-chain fatty acids and bacterial neurotoxic metabolites specifically with depression. Our results also show that microbiome and genetic factors explain self-reported mental health status and improvement better than demographic variables independently. The genetic and microbiome factors identified in this study provide the basis for designing and personalizing dietary interventions to improve mental health.

Preserved SARS-CoV-2 Vaccine Cell-Mediated Immunogenicity in Patients With Inflammatory Bowel Disease on Immune-Modulating Therapies.

Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications.

Incidence, outcomes, and impact of COVID-19 on inflammatory bowel disease: propensity matched research network analysis.

BACKGROUND: Accurate estimates for the risk of COVID-19 in IBD, and an understanding of the impact of COVID-19 on IBD course and the risk of incident post-infectious IBD are needed. AIMS: To estimate the risk of COVID-19 in IBD and study its impact on IBD course and the risk of incident post-infectious IBD. METHODS: A retrospective propensity score matched cohort study utilising multi-institutional research network TriNetX. COVID-19 patients with and without IBD were identified to quantify the risk of COVID-19 in patients with IBD, COVID-19 outcomes in patients with IBD and the impact of COVID-19 on IBD disease course. The risk of incident post-infectious IBD in COVID-19 patients was compared to the population not infected with COVID-19 during a similar time period. RESULTS: Incidence rate ratio for COVID-19 was lower in IBD patients compared to the non-IBD population (0.79, 95% CI: 0.72-0.86). COVID-19-infected patients with IBD were at increased risk for requiring hospitalisation compared to non-IBD population (RR: 1.17, 95% CI: 1.02-1.34) with no differences in need for mechanical ventilation or mortality. Patients with IBD on steroids were at an increased risk for critical care need (RR: 2.22, 95% CI: 1.29-3.82). Up to 7% of patients with IBD infected with COVID-19 suffered an IBD flare 3-months post-infection. Risk for incident IBD post-COVID was lower than that seen in the non-COVID population (RR: 0.64, 95% CI: 0.54-0.65). CONCLUSION: We observed no increase in risk for COVID-19 amongst patients with IBD or risk for de novo IBD after COVID-19 infection. We confirmed prior observations regarding the impact of steroid use on COVID-19 severity in patients with IBD.