Research

Environmental Enteric Dysfunction

Environmental enteric dysfunction (EED), also known as “tropical enteropathy,” is a leading barrier to achieving better growth and development in children living in low-resource settings, yet it “may be one of the costliest diseases you’ve never heard of, ” as observed by Bill Gates. Little is known about its etiology. Malnutrition compounded by fecal contamination of the environment leading to recurrent enteric infections is thought to contribute to EED, a disease characterized by leaky and inflamed intestines that absorb nutrients poorly. We have spearheaded research linking poor household environmental conditions, EED, and impaired growth. Within the WASH Benefits trial in Bangladesh, we measured the effects of integrating nutrition with WASH interventions on EED. We found reductions in gut permeability and inflammation during the first year of life, suggesting that the interventions promoted healthy intestinal maturation. Ultimately, these findings will advance our understanding of the biological underpinnings by which children develop EED and how these mechanisms adversely impact child thriving. To learn more, see our papers in Clinical Infectious Diseases and American Journal of Tropical Medicine and Hygiene.

Climate Change / Planetary Health

Pathogen exposure in animal feces is largely overlooked in mainstream WASH interventions. A joint WHO and UNICEF policy piece supported calls for transformative WASH, a set of “interventions that lead to a comprehensively clean environment” (e.g., through the management of animal feces, creation of safe play spaces, etc.) Although transformative WASH is the ultimate goal, a conventional piped water approach fails to address the challenges of climate change, population growth, and limited resources. Along with colleagues in Indonesia, Fiji, and Australia, we are addressing these issues through the RISE program, the objectives of which are to enable communities to create green space for food cultivation, recycle wastewater, harvest rainwater, restore biodiversity, and reduce vulnerability to flooding and climate change. The program is simultaneously conducting a pair of trials evaluating the health and economic benefits of a novel water-sensitive and nature-based intervention for managing WASH and floodwater in 24 informal settlements across Fiji and Indonesia. We are co-leading efforts to assess environmental enteric dysfunction, microbiome, enteropathogens, and antimicrobial resistance in young children. To learn more, see our papers in BMJ Open, Lancet Planetary Health, and Environment International.

Nutrition / Growth / Development

Globally, approximately 171 million children under five years of age are stunted and 250 million children are at risk of not fulfilling their developmental potential. In a pair of randomized trials in Kenya and Bangladesh, we assessed the effects of nutrition, water, sanitation, and handwashing interventions on anemia, micronutrient status, growth, and development. Infant and young child feeding counseling with lipid-based nutrient supplements reduced the risks of anemia, iron deficiency, and low vitamin B-12. We reported that the nutrition intervention improved growth in Bangladesh and Kenya; nutrition and WASH interventions reduced diarrhea in Bangladesh, but not in Kenya; and nutrition and WASH interventions improved child development at age two years in Bangladesh, but not in Kenya. Within the WASH Benefits studies, we are further investigating the complex connections between nutrition, the immune system, stress physiology, and EED in pathways leading to poor growth and development. To learn more, see our articles in American Journal of Clinical Nutrition and Current Developments in Nutrition.

Telomere Biology

Populations living in low-resource settings experience greater frequency and severity of adverse environmental, behavioral, and psychosocial exposures leading to higher disease burden and premature aging. The Developmental Origins of Health and Disease theory postulates that cumulative early life exposures have long-term consequences for disease and aging. Telomere length may predict disease and aging over the life course. Telomeres, DNA-protein complexes present at the ends of chromosomes, shorten during cell division and contribute to cell senescence. Little is known about early life telomere length trajectories in low-income countries and modifiable exposures that could lead to improvements in telomere health and aging-related outcomes. Prior literature has generally linked stress with shortened telomeres. We found that an integrated nutrition and WASH intervention shortened telomere length in children. These findings support an adaptive role for telomere shortening: active telomere length regulation may be the body’s strategy to address the increased energy requirements necessary for rapid growth during the first year of life. We then led a follow-on study that found a positive association between telomere length and child growth. Longer overall initial telomere length in the first two years of life could signal increased resilience and healthy growth trajectories. These novel studies question conventional interpretation of childhood telomere length in health, disease, and aging. To learn more, see our initial article in eLife and our follow-on article also in eLife.

Stress Physiology

Chronic stress, in the form of poverty, malnutrition, and infections, may cause irreversible harm if it begins during early childhood, a critical period of rapid growth and development. During this period of heightened plasticity, the neuroendocrine network develops and adapts in response to nutritional, psychosocial, and environmental exposures. A regulated stress response is essential to maintain healthy growth and developmental trajectories throughout life. We assessed the impact of a combined nutrition, drinking water, sanitation, and handwashing intervention on stress physiology and epigenetic programming. We led a study that found that integrated nutrition and WASH interventions were associated with adaptive responses, including reduced oxidative stress, enhanced cortisol reactivity, and reduced methylation levels in a transcription binding site of the glucocorticoid receptor gene. These findings may have critical implications for growth and development. To learn more, read our preprint on medRxiv.

Immune System Development

Understanding the interactions between immunoprotective, immunoregulatory, and immunopathologic responses, which form the immune triad during early childhood, is crucial as they may determine the ability of the individual to mount immunoprotective versus immunopathological responses, resist infectious diseases, and affect lifelong health. We led a study that found that an integrated nutrition, water, sanitation, and handwashing intervention enhanced Th2-driven immunoprotection and IL-10-driven immunoregulation, and suppressed the immunopathologic response. We envision that this study will inform prospective trials and scale-up of integrated nutrition and WASH interventions targeting physiological balance and optimization within the immune system during early childhood. We further posit that such optimization may ultimately enhance the potential for an individual’s growth and development. To learn more, read our preprint on medRxiv.

Pathogens / Microbiome

As described above, environmental enteric dysfunction (EED) is a multifaceted, subclinical disorder characterized by chronic gut and systemic inflammation, increased microbial translocation, and reduced nutrient absorption. Recurrent pathogen infections and microbiome dysbiosis may potentially serve a critical role in this disorder. We conducted a study characterizing the microbiome of children living in an urban informal settlement in Bangladesh. We led a randomized trial that showed that individual handwashing and sanitation interventions significantly reduced Giardia infections in young children living in rural Bangladesh. Because both interventions reduced Giardia prevalence by similar amounts, handwashing interventions could be a more cost-effective strategy than latrine construction to reduce Giardia infection in this setting. To learn more, see our papers in Clinical Infectious Diseases and PLOS One.