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

Abstract

Obesity is a significant health problem due to its profound health deteriorating effects and high costs for healthcare systems. There exist lifestyle and pharmacological interventions available to prevent and reverse obesity; however, at the population level, these have shown to be insufficient, and we continue to see a worldwide increase in obesity prevalence. The gut microbiome has been shown to influence the susceptibility to weight gain and difficulty in losing weight and to be associated with successful long-term weight loss. Therefore, multiple studies have suggested that obesity interventions should consider the gut microbiome as a primary target through an improved diet and a crucial endpoint to monitor. However, there is a paucity of evidence regarding how to tailor the diet for an individual's microbiome and what changes are expected to occur due to successful weight management. Digital therapeutics solutions have emerged as an exciting alternative to increase population access, reduce costs, and have the potential to accompany individuals on their health-promoting journey closely. Digbi Health has developed a dietary and lifestyle program to achieve weight loss that effectively reduces weight and improves diverse health outcomes by prioritizing and personalizing food ingredients to match an individual's genetic profile and nurture the gut microbiome. In this study, we analyze the weight loss pattern and microbiome profile of 103 individuals to identify the effects of the weight loss program on the gut microbiome between their baseline and follow-up samples. We found that 80% of individuals lost weight during the study. Analysis of their gut microbiome identified genera, functional pathways, and microbial communities associated with BMI changes and dietary and lifestyle program. The microbial genera and functional pathways associated with a reduction in BMI during the study include several previously reported in the literature, including Akkermansia, Christensenella, Oscillospiraceae, Alistipes, and Sutterella, short-chain fatty acid (SCFA) production and degradation of simple sugars like arabinose, sucrose, and melibiose. Network analysis identified two microbiome communities associated with BMI, one of which also significantly responded to the weight loss program, which includes multiple known associations with BMI and obesity. Our findings provide additional evidence for using the gut microbiome as an endpoint of weight loss program and highlight how it positively impacts the gut microbiome, with significant parallels in weight loss and health outcomes. These results provide additional evidence for known microbiome biomarkers of obesity and highlight new ones that warrant further research.