Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.07.18.665619

The impact of western versus agrarian diet consumption on gut microbiome composition and immune dysfunction in people living with HIV in rural and urban Zimbabwe

Abstract

BackgroundPeople living with HIV (PLWH) suffer from chronic inflammation even with effective antiretroviral therapy (ART). A high-fat, low-fiber western-type diet has been linked with inflammation, in part through gut microbiome changes. In sub-Saharan Africa (SSA), a region with high HIV burden, urbanization has been linked with a shift from traditional agrarian towards westernized diets, and with changes in food security. To explore the relationship between diet, inflammation, and the gut microbiome in PLWH, we enrolled 1) ART Naive PLWH who provided samples before and after 24 weeks of ART, 2) PLWH on ART at both timepoints and 3) HIV-seronegative controls. Individuals were evenly recruited from rural and urban Zimbabwe (locations were 145 kilometers/90 miles apart). Using a food frequency survey designed to measure intake of agrarian versus western-type food items in Zimbabwe, we determined how diet differs with urbanization, HIV-infection and treatment, and is related to inflammation and the gut microbiome. ResultsIndividuals residing in a rural area of Zimbabwe less frequently consumed high-fat, low-fiber western type food items and had lower consumption of diverse food items overall, except for sadza-a subsistence staple-processed from home-grown grains. Consumption of a more western-type diet correlated with lower CD4+ T cell percentage in untreated and treated PLWH and with increased T cell exhaustion in PLWH on ART. PLWH on ART at time of enrollment also consumed diverse food items at a lower frequency and more often were underweight. Low food consumption correlated with muted improvements in T cell exhaustion after 24 weeks of ART. Individuals residing in the rural area had more Prevotella-rich/Bacteroides-poor microbiomes, but this did was not significantly mediated by diet. western diet consumption reduced the diversity of carbohydrate substrate degradation capabilities in the microbiome, based on predictions made using metagenomic polysaccharide utilization loci. ConclusionsTaken together, this work supports that consumption of more high-fat/low-fiber type food items has the potential to exacerbate HIV pathogenesis in a sub-Saharan setting where HIV burden is high and reinforces the importance of nutritional support for promoting immunologic response to ART in PLWH in SSA.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Burkhart Colorado, A. S., Nusbacher, N., O'Connor, J., Marden, T., Higgins, J., Neff, C. P., Fiorillo, S., Campbell, T., Borok, M., Boyd, K. F., Sterrett, J. D., Palmer, B. D., Lozupone, C.. 2025-07-22. The impact of western versus agrarian diet consumption on gut microbiome composition and immune dysfunction in people living with HIV in rural and urban Zimbabwe. https://doi.org/10.1101/2025.07.18.665619

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗

Beta-lactam enhancement against methicillin-resistant Staphylococcus aureus by cell wall blockade is autolysis-dependent: a butyrolactone derivative as case in point

Methicillin-resistant Staphylococcus aureus (MRSA) is non-susceptible to beta-lactams. Blockade of cell wall biosynthesis is a potential target for beta-lactam enhancement but requires further investigation. A butyrolactone derivative enhanced beta-lactams against MRSA strains by reducing the availability of D-Ala-D-Ala. Unlike D-cycloserine, it did not inhibit D-Ala-D-Ala ligase (Ddl). Nor did it show an additive or synergistic effect when combined with cycloserine, indicating a unique mechanism for blocking cell wall precursor production that does not involve the traditional Lipid II pathway. Notably, beta-lactam potentiation by our chemical or D-cycloserine was highly dependent on the intrinsic autolytic ability of the tested MRSA strains. Strains that resisted lysis upon Triton X-100 exposure showed a minimal increase in beta-lactam susceptibility, whereas highly autolytic strains showed significant changes in their beta-lactam MICs. We have thus identified autolytic ability as the Achilles Heel in the strategy of targeting cell wall biosynthesis for beta-lactam potentiation.

microbiology↗

Rapid and largely reversible shifts in the canine fecal metabolome during dietary change

Diet can rapidly change the fecal metabolome, but less is known about recovery after the original diet is restored. We used untargeted UPLC-MS metabolomics to analyze 72 fecal samples from nine Pumi dogs during an owner-managed switch from dry food to raw food and back to dry food. Diet phase accounted for a large proportion of variation in both ionization modes. More than 13,000 LC-MS features changed at the first sampling point after the switch to raw food, with a similarly large response after return to dry food. Among features significant in both comparisons, more than 99% changed in opposite directions. At the final sampling point, no positive-mode (ESI+) features and only 13 negative-mode (ESI-) features differed from the second dry-food baseline under the same threshold. BARF-associated patterns persisted in analyses excluding individual dogs and in pedigree-adjusted candidate models, although individual feature effects depended on normalization. Putative metabolites from several biochemical classes differed in their response and recovery. The fecal metabolome therefore changed rapidly and returned largely toward baseline, with differences among dogs.

microbiology↗