Fiber, the Gut, Heart Disease and HIV

Investigators from Cedars-Sinai have made two important discoveries about fiber and the gut microbiome in patients with human immunodeficiency virus, or HIV.

Their findings, published today in the peer-reviewed journal Cell Reports, could aid future studies looking at the effects of diet and the microbiome, especially the process of fiber metabolism by gut microbes.

The team of investigators—led by Ivan Vujkovic-Cvijin, PhD, assistant professor in the department of Biomedical Sciences and department of Gastroenterology at Cedars-Sinai—are among the first to find that looking for fiber metabolites—molecules that strengthen gut barrier integrity and immune function—in blood samples, versus traditional stool samples, provides a more accurate representation of production of these metabolites by the gut microbiome.  

With this knowledge, investigators also discovered that gut microbial production of these fiber metabolites is related to the prevention of heart disease and death in people with HIV, the virus that causes acquired immunodeficiency syndrome (AIDS).

“This is an important step in the human microbiome field because the high-fiber diet has been shown to protect from a remarkable number of diseases, but the field has struggled to quantify the immediate effects of such diets,” said Vujkovic-Cvijin, corresponding and senior author of the study. “We anticipate our discovery will allow better quantification of microbial fiber metabolism and will lead to a greater understanding of the precise pathways that link fiber metabolites to protection from diseases and early death in people with HIV.”

People with HIV have long been known to experience higher rates of many diseases and premature death, despite being treated with optimal antiretroviral therapy. The medical field also knows, based on past studies from Vujkovic-Cvijin and team, that the gut microbiota of people with HIV is different from that of those who are HIV-negative.

This latest research sheds light on the “why.”

Investigators found that an abundance of microbial enzymes involved in fiber deprivation correlates more strongly with fiber metabolite levels in blood than in stool.

Through this research, the team also found that significantly higher levels of these microbial enzymes were found in people who did not later succumb to heart disease or death, suggesting the importance of this pathway in the health of people with HIV.

“Thanks to this important research, we now understand that a lack of ability of the gut microbiome to digest fiber precedes medical conditions like heart disease, suggesting this function of the microbiome may also contribute to their development,” said David Underhill, PhD, chair of the Department of Biomedical Sciences, who was not involved in the research study.

Underhill said future studies may also gain more information by examining blood levels of fiber metabolites, instead of examining stool samples.

“Blood samples appear to paint a clearer picture of who might best benefit from fiber, and which types,” said Underhill.

Looking ahead, Vujkovic-Cvijin also plans to focus future research efforts on the precise pathways that may link fiber metabolites to protection from disease and early death in people with HIV.

“There are several likely candidates, and we hope to uncover which of these pathways might have the greatest impact on health,” said Vujkovic-Cvijin.

Additional Cedars-Sinai authors include Alice Lo and Jacob Gifford. Other authors include Irini Sereti, Myrthe L. Verburgh, Anders Boyd, Eveline Verheij, Aswin Verhoeven, Ferdinand W.N.M. Wit, Maarten F. Schim van der Loeff, Martin Giera, Neeltje A. Kootstra, and Peter Reiss.  

DOI: 10.1016/j.celrep.2023.113336

Funding: Vujkovic-Cvijin was funded by the Crohn’s & Colitis Foundation Career Development Award. This work was supported in part by The Netherlands Organization for Health Research and Development and AIDS Fonds and by the intramural research program of NIAID/NIH.

Read more from the Cedars-Sinai Blog: Cedars-Sinai Investigators Exploring the Connection Between the Microbiome and Diabetes