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

Abstract

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.

Longitudinal gut microbial signals are associated with weight loss: insights from a digital therapeutics program

“…We did not find that the individual’s demographics or lifestyle factors analyzed influenced the weight loss (or gain) achieved between T1 and T2 (Table S1). This is in line with our previous scientific reports that show equitable results of Digbi’s weight loss program concerning the individual gender and age, among other socio-economic factors 25 .…”

“…In this context, the evidence presented in this and our previous studies supports this premise. It highlights microbial taxa and their functions that may be targeted to improve the gut microbiome composition with concomitant positive effects in health outcomes, including obesity, cardiovascular health, mental health, and functional gastrointestinal disorders [23][24][25][26] . Interestingly, 9 out of the 18 genera associated with BMI also changed their abundance in a pattern consistent with the beneficial effect of the weight loss program on the gut microbiome.…”

“…Digbi Health has developed a digital therapeutics program based on the participants' multi-omic signals (genetics and gut microbiome), along with self-reported data and data from wearable devices. The outcomes of the weight loss program in different cohorts of individuals have been recently published, demonstrating its applicability not only in weight loss 23 , but also in reducing fasting blood glucose and HbA1c levels 24 , improving mental health symptoms 25, and functional gastrointestinal disorders 26 .…”

Digital therapeutics in the clinic

“…DTx have shown promise in various disease areas including psychiatric, [36][37][38] cardiovascular, 29,39 metabolism, 40 gastrointestinal, 41 neurodevelopmental, 33,42 and neurological diseases, 43,44 among others. With such a broad application, DTx hold great potential in translatability and treatment across different disease areas among the general population.…”

“… 27 , 28 The software can be further divided into subtypes such as mobile applications, 29 web applications, 30 , 31 virtual reality (VR), 32 AI, 33 , 34 video games, 35 and approved devices, among others. DTx have shown promise in various disease areas including psychiatric, 36 , 37 , 38 cardiovascular, 29 , 39 metabolism, 40 gastrointestinal, 41 neurodevelopmental, 33 , 42 and neurological diseases, 43 , 44 among others. With such a broad application, DTx hold great potential in translatability and treatment across different disease areas among the general population.…”