Rachel N. Carmody, Ph.D. - US grants

All human societies regularly process their foods by thermal and non-thermal means. This feature distinguishes humans from other species, and may even be compulsory from an energetic perspective, given that we possess relatively small molars and gastrointestinal tracts that commit us to an easily digestible diet. Yet the energetic significance of food processing and its evolutionary implications have barely been considered. This study tests the hypothesis that thermal and non-thermal processing lower the metabolic cost of food digestion, known as diet-induced thermogenesis (DIT). Effects will be evaluated for tubers and meat, foods widely exploited by humans and believed to have been critical resources for ancestral hominins. In theory, processing of these foods should result in a loss of structural integrity that lowers DIT due to reduced chewing and gastric effort, as well as increased access by digestive acids and enzymes. Since heat should weaken food structural integrity to a greater extent by gelatinizing starch and collagen, it is further predicted that the effects of thermal processing will exceed those of non-thermal processing. To evaluate these predictions, energy expenditure data are collected via respirometry from subjects before and after standardized meals served raw and whole, raw and pounded, roasted and whole, or roasted and pounded, based on a counterbalanced within-subjects design. Rats will be used as model organisms in the interests of low cost and high control, but a subset of trials will be replicated using human subjects to validate the animal model.

This study will quantify the impacts of thermal and non-thermal processing on DIT, an important factor in energy balance. Results will improve our understanding of the energetic returns of food processing and inform models of hominin transitions toward higher dietary quality. Low DIT has been implicated as a factor in the development of obesity. By determining the effects of food processing on DIT, this research contributes basic data that could help consumers influence the partitioning of meal energy to metabolism versus body stores. Results will thus be communicated broadly to peer-reviewed journals and conferences in anthropology and nutrition, as well as public forums. This doctoral dissertation research project will also contribute to the professional development of a female graduate student.

DESCRIPTION (provided by applicant): The trillions of microorganisms inhabiting the human gastrointestinal tract (gut microbiota) contribute importantly to energy balance, but their net effect on energy gain and expenditure is shaped by diet. While the impacts of altering diet quantity or composition have been studied, the impacts of processing a given diet by common methods like cooking or grinding remain unknown. A large literature indicates that food processing enhances energy gain by increasing the proportion of dietary carbohydrates that are assimilated in the small intestine. This reduces the fraction of nutrients passing undigested into the colon, where the densest microbial communities reside, and could thus be expected to limit the microbial contribution to energy gain. However preliminary data reveal dramatic impacts of a processed carbohydrate-rich plant diet on gut microbial ecology that instead favor microbial taxa known to stimulate host adiposity. These results, combined with those of prior studies, suggest that energy gain reflects complex interactions between host, dietary and microbial factors. This goal of this research program is to characterize the contributions of the gut microbiota to energy gain on processed diets. Benefiting from insight achieved in the comparison of conventional and gnotobiotic (germ-free or colonized) mice, the studies proposed will address three specific aims: Aim 1: Test alternative hypotheses for the impact of food processing on gut microbial communities, focusing on the roles of processing in increasing bioavailability and deactivating foodborne xenobiotics; Aim 2: Interrogate the microbial promotion of energy gain on processed diets through gnotobiotic experiments involving colonization and gut microbiota transplantation; and Aim 3: Extend work to other food substrates that exhibit distinct properties when processed, enabling tests of other putative mechanisms for the microbial promotion of energy gain. These studies will address novel mechanisms of host-microbial interaction, increasing our understanding of the ecological determinants of human health. Such work holds clinical promise because robust knowledge of microbial impacts on host physiology could lead to new treatments for disease via manipulation of the gut microbiota or its downstream host targets. Notably, food processing is an especially attractive possibility for intervention, being a ubiquitous and readily modifiable feature of the human diet. These advantages make this research program a fertile foundation for subsequent work involving a wide range of substrates and processing methods, more detailed analysis of host-microbial interactions, and eventual translation to human subjects.

Nutritional and energetic models of human metabolism assume that all dietary fats have the same caloric value. However, recent developments in gut microbiome research have challenged this view, with gut microbial communities shifting in response to different fat-rich diets, and the resulting gut microbiota differentially impacting energy gain. This dissertation project will examine the role of dietary fat types on energy gain from a human holobiont perspective, which interrogates both host and microbial mechanisms of energy harvest from different dietary fat sources. By assessing the impact of dietary fat type on host-microbial interactions, the investigators aim to better understand the process of dietary fat metabolism in ancestral and modern humans, to challenge traditional models of the isocaloric nature of fats, and to gain insight into associations between dietary fat intake and increasing rates of metabolic disease in industrial populations. Apart from contributing to the peer-reviewed scientific literature, this research will facilitate undergraduate research opportunities, particularly for women and underrepresented minorities in science, who presently comprise 80% of the laboratory research staff. In addition, through connections with the Harvard T.H. Chan School of Public Health and the Harvard Museums of Science and Culture, the investigators have committed to contributing to programs that make science accessible for a broad public audience.

The trillions of microbes that reside in the human gut are now understood to play important roles in digestion and energy regulation. However, to date, models of past and present human energy budgets have not considered the microbial contributions to energy harvested from diet. In this research, the investigators will probe mechanisms of dietary fat metabolism that involve both host and microbial processes, evaluating the impacts of different dietary fats on host energy budget, intestinal fat absorption and inflammation, gut microbial composition, and direct gut microbial contributions to host energy status. To address these processes, the investigators will use conventional and germ-free murine models, which are routinely used for studying the effects of microbial community shifts on human physiology. This research will clarify the role that different dietary fats have played in the evolution of human energy metabolism, and will suggest new pathways for targeting the high and rising rates of obesity, type II diabetes, and other metabolic diseases in the industrialized world.

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.