Gut Microbiome of Helminth Infected Indigenous Malaysians Is Context Dependent

Abstract

While microbiomes in industrialized societies are well characterized, indigenous populations with traditional lifestyles have microbiomes that are more akin to those of ancient humans. However, metagenomic data in these populations remains scarce and the association with soil-transmitted helminth infection status is unclear. Here, we sequenced 650 metagenomes of indigenous Malaysians from 5 villages with different prevalence of helminth infections. Individuals from villages with higher prevalence of helminth infections have more unmapped reads and greater microbial diversity. Microbial community diversity and composition were most strongly associated with different villages and the effects of helminth infection status on the microbiome varies by village. Longitudinal changes in the microbiome in response to albendazole anthelmintic treatment was observed in both helminth infected and uninfected individuals. Inference of bacterial population replication rates from origin of replication analysis identified specific replicating taxa associated with helminth infection. Our results indicated that helminth effects on the microbiota was highly dependent on context and effects of albendazole on the microbiota can be confounding for the interpretation of deworming studies. Furthermore, a substantial quantity of the microbiome remains undescribed and this large dataset from indigenous populations associated with helminth infections should facilitate characterization of the disappearing microbiome from developed industrialized societies.

Clostridia isolated from helminth-colonized humans promote hatching of Trichuris muris

“…The helminth prevalence in the Orang Asli population decreased from 67.2% at baseline to 22.5% 21 days after treatment. The helminth prevalence in the urban control population was 0% (Tee et al , 2022). To identify helminth associated bacteria, we determined which OA isolates were enriched in pre-ABZ samples compared with post-treatment and urban control samples.…”

“…We also included two Bacteroidales species, Bacteroides thetaiotaomicron and Bacteroides vulgatus , which are ubiquitous anaerobes in the human microbiome. In addition, B. vulgatus growth rate was negatively correlated with Trichuris egg burden in the Orang Asli (Tee et al , 2022). We show representative high and low hatching conditions as a time course (Figure 4B) and the full dataset as bar graphs at individual time points (Figure 4C-E) to facilitate visualization.…”

“…Whole genome sequencing of the OA isolates and the availability of the largest Malaysian microbiome dataset to date (Tee et al , 2022) allowed us to uncover differential and high-resolution relationships between specific taxa and helminth colonization. Genomes corresponding to OA isolates were enriched in Malaysian metagenomes compared with HMP, yet only a subset of isolates decreased in the microbiomes of individuals treated with deworming medication.…”

“…Sample collection and processing for the large Orang Asli and Kuala Lumpur cohort which provided metagenomes for our analyses is described in (Tee et al , 2022). In brief, fecal samples were collected from Orang Asli villagers right before administration of albendazole (ABZ) at 400mg/day for 3 consecutive days and follow-up samples were collected after 21 days.…”

“…Study exclusion criteria consisted of pregnant women, breastfeeding mothers and presence or perceived presence of any clinically significant disease. Information about human subjects from the large Orang Asli and Kuala Lumpur cohort which provided metagenomes for our analyses is described in (Tee et al , 2022).…”