Doctoral Dissertation Research: Physiological tradeoffs arising from early-life disruption of the gut microbiome

Harvard University, Cambridge MA

Investigators

Abstract

The gut microbiome – the term used to refer to the collective community of microbes that live in the gastrointestinal tract – is a key player in the creation and use of energy for the host. Studies show that disrupting the course of development of the gut microbiome with antibiotics can increase body fat and the linked risk of obesity and disease later in life. These effects can differ between females and males. This doctoral dissertation research investigates how antibiotic use causes increased body fat, frames this effect in an evolutionary context, and examines why sex differences in this effect arise. Combining these areas of focus allows this investigation of cause-effect relationships important for understanding how factors experienced in early life impact health outcomes later in life, and in addition to the potential to inform public health research, the results speak to larger theoretical frameworks in biological anthropology. This research provides intensive training for a female graduate student and opportunities for undergraduate students, particularly members of groups currently underrepresented in STEM fields to gain robust research experience. Environmental adversity during early life can cue developmental changes in young animals that promote metabolic diseases in adults such as obesity. The gut microbiome plays critical roles in the regulation of host energy balance, with disruption of the gut microbiome through antibiotic use causing short-term weight and fat loss. Notably, despite short-term energy losses, exposure to antibiotics in early life has been linked to obesity and overweight in adulthood in humans, mice, livestock, and other animals. However, the physiological mechanisms underlying these long-term obesogenic effects remain unclear. The investigators hypothesize that gut microbiota depletion during the critical period of early life constrains energy budgets, necessitating energy allocation tradeoffs that persist in adulthood at the cost of fitness. To test this hypothesis, the investigators profile the gut microbiome and host energy allocation over the course of development in a conventional mouse model of early-life antibiotic treatment, followed by direct evaluation of immune and reproductive fitness in adulthood. The proposed study provides novel evidence linking disciplines concerned with the developmental origins of health and disease to those concerned with the gut microbiota and host-microbial interactions. The results of this research contribute to theoretical discussions regarding trade-offs following early life influence and illuminates the factors contributing to rising rates of metabolic diseases across the globe. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.