Diet and microbiome are important factors to consider for people living with HIV (PLWH). Different dietary habits interact with different microbiome compositions, and thesevariables may mediate health outcomes for PLWH.
Catherine Lozupone, PhD, professor of biomedical informatics at the University of Colorado Anschutz (CU Anschutz), conducts extensive research on the interactions between the human microbiome, diet and disease. Lozupone has conducted research on how these interactions affect PLWH—specifically exploring how dietary habits and the composition of a person's microbiome can mediate health outcomes for PLWH.
Lozupone and her team in the Lozupone Lab, in collaboration with researchers at the CU Anschutz Department of Medicine, recently published a paper in the Microbiome journal sharing their recent study that explored the impact of diet on gut microbiome composition and immune dysfunction in PLWH in both rural and urban Zimbabwe.
Around 70% of the global HIV epidemic is concentrated in sub-Saharan Africa. Additionally, low- and middle-income countries in this region have shown some transition towards different dietary habits, specifically the consumption of more “western” types of foods, but also can be exposed to higher rates of malnutrition due to food insecurity. These factors, in combination with other nuances, make sub-Saharan Africa an important locale for studying the relationships between diet, microbiome and health for PLWH.
A traditional diet in sub-Saharan Africa would be known as an agrarian diet: a diet that tends to be higher in fiber and grains and lower in fat, sugar and processed foods.
These agrarian diets are in contrast to what is often referred to as a “western diet:” a diet that is lower in fiber while being higher in fat, processed sugar, sodium and refined/processed foods.
Although agrarian diets would be considered more 'traditional’ in sub-Saharan Africa, there has been a transition towards the consumption of more “western” type foods—especially in developing urban areas. In this study, Lozupone and her team explored how these differing diets might affect immune function and chronic inflammation in PLWH, predicting that the microbiome would play a mediating role.
The team examined the impacts of different lifestyle factors such as dietary habits (agrarian vs. western) and living location (rural vs. urban)—focusing on how these factors affect the microbiome and biomarkers associated with HIV health outcomes. This study examined these relationships across three specific cohorts of people:
1. The ART Naïve group, which contained PLWH who were not yet being treated with a specific Antiretroviral Therapy (ART) treatment at the start of the study, but subsequently began treatment;
2. The ART Experienced group, which contained PLWH who were already being treated with this specific ART treatment at the start of the study; and
3. The control group, which contained only people without HIV.
ART was delivered concurrently with the antibiotic cotrimoxazole to prevent opportunistic infections, which is common standard of care in sub-Saharan Africa. Fecal and blood samples were collected from study participants during two clinic visits that were 24 weeks apart. Fecal samples were used to evaluate microbiome composition and blood samples to evaluate immune markers.
To evaluate the participants’ dietary habits, the researchers created a Food Frequency Questionnaire (FFQ) that specifically examined the degree to which the participantsconsumed a more agrarian vs. a more western diet by categorizing and coding specific types of foods. For example, in the ‘Grains’ category, white rice was coded as ‘western,’ while sadza—a traditional whole grain meal popular in Zimbabwe—was coded as ‘agrarian.’
Overall, the researchers found that individuals living in rural Zimbabwe tended to consume less “western diet” type food items and far more “agrarian” foods. The team also found that people in the rural areas reported eating diverse foods less frequently, as did PLWH on long-term ART, suggesting that they were more vulnerable to food insecurity.
Consumption of a more “western” type diet was correlated with a lower CD4+ T cell percentage in untreated PLWH participants. These CD4+ T cells are a vital component of the immune system, but they are often disrupted or eliminated by HIV infection. This could suggest that a more “western” type diet has the potential to exacerbate the impact of HIV on immune function.
The researchers also found that, for the ART Experienced cohort, a more “western” type diet was positively correlated with CD8+PD1+ T cells. CD8+ T Cells are another important component of the immune system that identify and eliminate toxic cells. When these cells express PD1, it suggests the cells have been working for a long time, which suggests what is known as “immune exhaustion.” This finding suggests that PLWH who are receiving ART treatment may display more immune exhaustion when consuming a more “western” type diet.
In a paper previously published by the Lozupone lab conducted on this cohort, the team had found that PLWH in urban Zimbabwe—but not rural Zimbabwe—had reductions in CD8+T cell exhaustion with treatment. These findings suggested that people in rural Zimbabwe were not experiencing the same degree of immunologic recovery.
In the study just published, the team found that the degree of improvement in CD4+ T cell exhaustion with treatment was dampened in people with low food consumption.
“These findings indicate that food insecurity is also an important aspect to consider for the health of people living with HIV in Zimbabwe,” said Lozupone. “This suggests that ART should be coupled with nutritional support to prevent malnutrition, particularly in rural areas that appear to be more vulnerable.”
In sub‑Saharan Africa, antiretroviral therapy (ART) is routinely administered alongside prophylactic cotrimoxazole to prevent opportunistic infections, and this cohort followed this practice. However, antibiotics alone have been shown to have a large impact on the gut microbiome, so it was important to evaluate the differences between cohorts.
In the Lozupone lab’s earlier study on the same population, the combination of ART plus cotrimoxazole was shown to exert a more substantial impact on gut microbiome structure than HIV infection itself. This treatment produced a notable reduction in overall microbiome diversity (alpha diversity), and also led to broad compositional shifts in microbiota.
Even so, the makeup of the gut microbiome was more strongly linked to immune problems—like T cell activation and exhaustion—in people who had not yet started HIV treatment, even though their microbiome changes were smaller.
“This is likely related at least in part to people with untreated infection having particularly strong defects in intestinal barrier function, which is partially remediated with ART,” said Lozupone. “In this recent study, diet had some relationship with microbiome compositional differences, but not necessarily in expected ways, and it was not a clear mediator of the diet:immune correlates.”
The results of this study suggest that consumption of a more “western” diet (as opposed to a more agrarian diet) can impact people with HIV, specifically how HIV infection can progress and damage the body. The results also suggest that food insecurity is an important consideration for the treatment of PLWH.
The team’s continuing research in Zimbabwe has also uncovered some of the microbiome mechanisms mediating diet, immune function and health with PLWH, such as how untreated HIV contributes to challenges with intestinal barrier function, or how ART treatment combined with antibiotics like cotrimoxazole can create large changes in microbiota.
These findings contribute to a growing body of evidence that suggests diet is an important consideration for PLWH, and that dietary intervention may be supportive in addition to established ART intervention.