The Far-Reaching Effects of Health Disparities on the Gut Microbiome and Health

Speakers at Digestive Disease Week 2022 presented research on how health disparities and socioeconomic factors can contribute to changes in the gut microbiome that have implications for cancer risk, immune health, and overall well-being.

Moderator Jasmohan S. Bajaj, MD, introduced the session by calling it “a cross-cultural, cross-microbial set of topics,” and Lisa Tussing-Humphreys, PhD, RD, University of Illinois Cancer Center, kicked it off with her presentation on the role of structural violence and racial inequities in colorectal cancer (CRC) risk. She showed a map of Chicago in which neighborhoods with lower socioeconomic status and higher proportions of people of color tend to have greater CRC incidence and mortality rates.

Tussing-Humphreys explained that levels of hydrogen sulfide microbes in the stool are higher in patients with CRC, which may indicate the potential role of diet in cancer risk, as high-fat diet increases the abundance of sulfidogenic bacteria. Research by the Chicago Colorectal Cancer Consortium—a multidisciplinary, multicenter effort to enroll individuals from across the city and collect data and laboratory samples—revealed that Black race was the strongest variable associated with sulfidogenic bacteria. However, race is a social construct, so Tussing-Humphreys and her colleagues propose that a latent variable such as structural violence could explain this difference. Their work aims to integrate the socioenvironmental context into the science.

Indeed, unpublished work from Tussing-Humphreys and colleagues shows that concentrations of hair cortisol, a marker of chronic stress, are much higher in Black individuals, particularly those with adenoma. This finding could indicate activation of the hypothalamic-pituitary-adrenal axis, which is thought to be a component in the pathway of CRC development.

By combining geospatial analysis, metagenomic data, glucocorticoid levels, and more, she hopes that the team’s research can help in “integrating these very distinct but important data sets together to really understand how a person’s environment can be contributing to disparities and how this is mediated through the gut and specifically the gut microbiome.”

Next, presenter Erika Claud, MD, UChicago Medicine, invited the audience to step into her world of neonatology to understand how disparities and the microbiome are linked. Preterm babies are at high risk of morbidities such as necrotizing enterocolitis that are inflammatory in nature and clearly associated with the microbiome. “You have disparities associated with just being born early, you have a risk of morbidity, and this is all before you’ve even left the hospital,” she said.

The risk continues into early childhood, as an association exists between the microbiome and neurodevelopment by age 2 years. Claud highlighted data from the UChicago subset of the Microbiome in Neonatal Development, or MIND, Cohort, which suggest that the microbiome composition has a significant role in head circumference growth. Additionally, the Nutrition and Pregnancy Study, a cohort of full-term Black babies born in Chicago, revealed the existence of 2 community types associated with different microbiome composition and also different outcomes in terms of infant cognition and language scores in boys.

Future directions for research will include analysis of microbiome samples from the MIND Cohort after discharge from the neonatal intensive care unit and ongoing investigation of the microbiome and neurodevelopment in mouse models. Claud suggested that this research points to the potential of “healthy disparities,” in which a stronger microbiome confers positive effects on future outcomes. No research team can solve poverty or give every infant a supportive home, but “if the microbiome is the ‘how,’ then we can start working on its role in neuroprotection.”

Marie-Claire Arrieta, PhD, of the University of Calgary, continued the discussion of the microbiome by explaining how the modern industrialized lifestyle has altered microbiota changes, which can be detrimental. Her presentation delved into the social structures that can drive the microbial exposure associated with disorders including multiple sclerosis, Crohn disease, and asthma.

According to Arrieta, a study conducted in Canada revealed 4 microorganism species that are reduced in children who went on to develop atopic wheeze, and an Ecuadorian study showed an increase in allergies and asthma observed when the setting underwent a transition from rural to semi-urban. The dysbiotic patterns associated with these disorders differed between the Canadian and Ecuadorian infants, so strategies to improve health outcomes through the microbiome need to take the part of the world into consideration.

The genetic factors in the microbiome appear to be a minor piece of the puzzle, Arrieta continued, as immigration to the United States is associated with a loss of gut microbiome diversity—an increase in Bacterioides strains and a decrease in Prevotella strains and fiber-degrading enzymes—that increases with obesity and is compounded across generations.

“The infant microbiome develops as a response to many factors including nutrition, medication, and the built-in environment, but it’s also really important to consider other factors that are above that umbrella, including socioeconomic status and the political and economic policies that lead to it,” Arrieta concluded.

Finally, Tien Dong, MD, PhD, of the University of California Los Angeles, presented an abstract on how discrimination literally “gets under the skin” by affecting the brain-microbiome-immune system axis. His team’s research revealed associations between self-reported feelings of everyday discrimination and negative health outcomes, but it also showed differential activation of various brain networks associated with discrimination across races.

Discrimination based on race, which can start from early childhood, may result in a chronicity of feeling discriminated against that can uniquely influence the brain-microbiome axis, Dong explained. “We hope that by looking at this multimodal aspect of how discrimination affects the body as a whole, we can better understand how discrimination leads to negative health outcomes,” he concluded.