UNIVERSITY PARK, Pa. — Jessica Grembi, an assistant professor of pharmacology in Penn State's College of Agricultural Sciences, has received a $500,000 grant from the Gates Foundation to investigate the role of the microbiome in environmental enteropathy — a condition characterized by inflammation of the small intestine that affects nutrient absorption.
The condition mainly occurs in low- and middle-income countries, and it can be especially detrimental to young children, potentially leading to growth and cognitive impairments, according to Grembi.
The study will use a new technology to identify biomarkers for environmental enteropathy in pregnant women living in these low- and middle-income countries, with the goal of using the findings to support the development and evaluation of maternal microbiome interventions.
“The general hypothesis is that the condition comes from chronic, low-grade exposure to pathogens that the intestines respond to with inflammation, which then hinders nutrient absorption,” Grembi said. “We want to learn more about the environment in the small intestine so we can be better informed to develop treatments, and to confirm whether pathogens are really the key players.”
She added that while traditional diagnostics such as blood tests might be able to pick up on systemic inflammation, and biomarkers in stool give us a picture of large intestine inflammation, they’re less able to focus on the small intestine in particular, which is vital to learning more about the condition.
This study will use a new technology called CapScan to gather samples directly from this part of the gastrointestinal tract in 240 pregnant women living in Bangladesh, Pakistan, Senegal and Zambia. CapScan is a capsule that is swallowed and is timed to unravel once it reaches the small intestine, where it can gather fluid to be tested later.
“Environmental enteropathy was originally diagnosed via biopsy in Vietnam veterans and Peace Corps volunteers returning to the U.S.,” Grembi said, noting that only the very upper part of the small intestine is accessible via biopsy, and the procedure must be done when the patient has fasted and often has been given sedatives to help them relax. “This is not an accurate picture of what the host and microbiota are doing during when a meal is being digested. And invasive biopsy procedures are difficult to do in the low- and middle-income countries where the condition is prevalent. This new technology allows us to sample during normal digestion in larger numbers of individuals and is providing us insight into what’s happening directly at the site where this condition is occurring.”
After collecting samples, the researchers will analyze and sequence them to better understand the small intestine’s environment and microbiota.
The team will measure host immune response, such as the amount of secreted antibodies in the small intestine and which bacteria the antibodies are targeting, as well as cytokines and other immune factors indicative of inflammation. They will look for associations between the abundance of specific microbes and the markers of inflammation to determine which bacteria might be important mediators of the condition.
The grant is part of Grembi’s ongoing efforts to learn more about environmental enteropathy and its effects on children and pregnant women.
Her previous research has evaluated the impact of water, sanitation, hygiene and nutrition interventions on reducing pathogen exposure and environmental enteropathy for children in rural Bangladesh; the influence of temperature and precipitation on diarrheal disease and specific pathogens; and the role of human and environmental microbiomes in disease states.
Her most recent work investigated the human small intestine microbes and metabolites in a nonperturbed state using the CapScan device in healthy individuals.
This past summer, Grembi visited one of the study field sites in Bangladesh, where the project is led by collaborators at the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Joining her on the trip was Nazifa Tabassum, a dual-title doctoral student in molecular, cellular and integrative biosciences and in microbiome sciences at Penn State.
While there, Grembi and Tabassum saw the field team in action during hospital and household visits, observing physicians, biostatisticians, anthropologists and biochemists as they worked with study participants, used the CapScan technology and processed the samples.
“icddr,b is a phenomenal partner in this work — it was inspiring to be among a team of researchers dedicated to meaningful health improvements within this community, as well as to be in a place where so many talented individuals have devoted their efforts for over half a century,” Grembi said of the team working in the community of Matlab, where the centre has been conducting health and demographic surveys, providing health care and conducting research on diarrheal diseases such as cholera since the 1960s. “Witnessing their commitment to advancing public health and the rich legacy of research was truly uplifting and an amazing experience to share with a mentee.”
The researchers also met the study participants themselves, an experience Tabassum said helped underline the importance of their work.
“My work is currently very computational — I work with data here in the U.S. where I can't see the physicians or patients on the other side of the world,” she said. “So, getting to meet them face to face was a reminder that there's a mom who's enrolling in the study, there's a person collecting and processing the samples. It put a face to the process.”
Grembi said samples from Bangladesh and the other field sites will arrive at Penn State over the next two to four months.
“This work brings us closer to understanding the gut environment where environmental enteropathy actually occurs, with the potential to inform real-world interventions for mothers and their babies,” she said.