Ambient long-term exposure to organophosphorus pesticides and the human gut microbiome: an observational study Original paper

What was studied?

This observational study examined ambient long-term organophosphorus pesticide exposure gut microbiome signatures in humans living in California’s heavily agricultural Central Valley, asking whether chronic residential exposure to organophosphorus (OP) pesticides is linked to measurable shifts in gut microbial composition and microbial metabolic potential. Participants provided fecal samples for 16S rRNA sequencing, and investigators inferred functional capacity using PICRUSt2 to generate predicted enzyme and MetaCyc pathway profiles. OP exposure was estimated using a geographic information systems approach that linked California Pesticide Use Reports to each participant’s residential history, calculating average OP application within a 500-meter buffer over the 10 years before stool collection (with additional 0–5 and 6–10 year sensitivity windows). The primary outcomes were alpha diversity (Shannon index), beta diversity (Bray–Curtis dissimilarity), differential abundance of taxa (family/genus), and differential predicted pathway abundance, with multivariable adjustment for age, sex, race, Parkinson’s disease (PD) status, pesticide co-exposures, and sequencing platform.

Who was studied?

A total of 190 adults were recruited from the Parkinson’s, Environment and Gene (PEG) study in Kern, Tulare, and Fresno counties. The cohort was older (mean age ~72 years) and included both PD cases (61%) and community/household controls (39%). Participants were predominantly White (74%) and slightly more often male (53%). Individuals with major gastrointestinal disease, immunocompromised states, or recent/ongoing antibiotic use were excluded to reduce non-exposure-related microbiome disruption. Using the study’s exposure definition, 36 participants (19%) were classified as “high OP exposure” (exposed to >1 OP chemical above the non-PD median), while 154 (81%) were low/no exposure. This design offers strong exposure characterization for ambient agricultural drift but limits generalizability to younger, healthier populations.

Most important findings

At the ecosystem level, OP exposure was not associated with bacterial alpha diversity or overall community structure (beta diversity). However, functional potential shifted: predicted metagenomes were less even/sparser in highly exposed participants (p=0.04), suggesting altered microbial gene-expression potential despite stable diversity metrics. Differential abundance analyses identified changes in two families and 22 genera, with many signals within Lachnospiraceae and Ruminococcaceae (Clostridia), including increases in Sellimonas, Blautia, Coprococcus_1, and multiple Ruminococcaceae UCG taxa, and decreases in Dialister, Anaerotruncus, Turicibacter, Parasutterella, and Cloacibacillus. Predicted pathways (34 total) suggested increased activity in cell-wall biogenesis and carbohydrate utilization (e.g., teichoic acid biosynthesis, peptidoglycan maturation, fucose degradation) and increased methanogenesis from acetate, while vitamin/cofactor pathways decreased, notably thiamin diphosphate (B1) and pyridoxal-5′-phosphate (B6) biosynthesis/salvage. These functional shifts point toward a microbiome adapting to chronic toxicant stress with changes in energy metabolism and structural reinforcement.

Key implications

For clinicians and microbiome signature databases, the main takeaway is that chronic ambient OP exposure may produce a “functional dysbiosis” phenotype—subtle taxonomic rearrangements (especially among SCFA-associated Clostridia lineages) coupled with predicted pathway changes affecting microbial respiration, cell-envelope biosynthesis, and vitamin metabolism—without collapsing overall diversity. This pattern aligns with a plausible long-term toxicant-adaptation signal rather than acute disruption. Clinically, it supports integrating environmental exposure history (especially agricultural proximity) when interpreting microbiome profiles in older adults and neurodegenerative populations, while underscoring that these findings are associative, predicted (not measured metagenomics/metabolomics), and derived from an older cohort with substantial PD prevalence.

Citation

Zhang K, Paul K, Jacobs JP, Cockburn MG, Bronstein JM, del Rosario I, Ritz B. Ambient long-term exposure to organophosphorus pesticides and the human gut microbiome: an observational study.Environmental Health. 2024;23:41. doi:10.1186/s12940-024-01078-y