Replication of Host St6galnac1-Microbiome Association Across Distinct Experimental Conditions in Heterogeneous Stock Rats
- 1Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Abstract
The gut microbiome is shaped by both environmental and host genetic factors. Identifying specific host loci is essential for understanding the heritability of microbiome-associated traits. The gene St6galnac1 encodes a sialyltransferase involved in mucin O-glycosylation. Tonnele et al. (2025) identified significant associations between a locus containing St6galnac1 gene, and the abundance of genus Paraprevotella using cecal samples collected from fasted animals. This association was replicated across three cohorts and paralleled with association found in humans between a functionally related sialyltransferase gene ST6GAL1 and Paraprevotella. Given the sensitivity of microbiome analyses to factors including sampling site, feeding status, and analytical framework, independent replication of these findings is important and it is also important to know if the association generalizes across other conditions or is highly specific to certain environments. Here, we performed a replication analysis using stool (not cecal) samples from 174 HS rats that were not fasted prior to collection. Stool samples underwent 16S rRNA gene sequencing, and microbial community structure was analyzed using compositionally aware methods. The rats were genotyped at the top SNP that was associated with Paraprevotella in the Tonnele et al. (2025) study. The association between genotype and Paraprevotella abundance was tested using a linear mixed model accounting for sex, cohort, and genetic relatedness. We successfully replicated (p=0.015) St6galnac1 - Paraprevotella association. These findings support the robustness of the St6galnac1 - Paraprevotella association across different sampling strategies and experimental conditions.
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BibTeX
@misc{sadegi2026replication,
title = {{Replication of Host St6galnac1-Microbiome Association Across Distinct Experimental Conditions in Heterogeneous Stock Rats}},
author = {M. Sadegi and B. B. Johnson and T. M. Sanches and G. Ang and J. Cao and M. Ambre and M. Brennan and O. George and R. Knight and A. Baud and A. A. Palmer and O. Polesskaya},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.758003},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.758003v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Replication of Host St6galnac1-Microbiome Association Across Distinct Experimental Conditions in Heterogeneous Stock Rats
AU - M. Sadegi
AU - B. B. Johnson
AU - T. M. Sanches
AU - G. Ang
AU - J. Cao
AU - M. Ambre
AU - M. Brennan
AU - O. George
AU - R. Knight
AU - A. Baud
AU - A. A. Palmer
AU - O. Polesskaya
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.758003
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.758003v1
AB - The gut microbiome is shaped by both environmental and host genetic factors. Identifying specific host loci is essential for understanding the heritability of microbiome-associated traits. The gene St6galnac1 encodes a sialyltransferase involved in mucin O-glycosylation. Tonnele et al. (2025) identified significant associations between a locus containing St6galnac1 gene, and the abundance of genus Paraprevotella using cecal samples collected from fasted animals. This association was replicated across three cohorts and paralleled with association found in humans between a functionally related sialyltransferase gene ST6GAL1 and Paraprevotella. Given the sensitivity of microbiome analyses to factors including sampling site, feeding status, and analytical framework, independent replication of these findings is important and it is also important to know if the association generalizes across other conditions or is highly specific to certain environments. Here, we performed a replication analysis using stool (not cecal) samples from 174 HS rats that were not fasted prior to collection. Stool samples underwent 16S rRNA gene sequencing, and microbial community structure was analyzed using compositionally aware methods. The rats were genotyped at the top SNP that was associated with Paraprevotella in the Tonnele et al. (2025) study. The association between genotype and Paraprevotella abundance was tested using a linear mixed model accounting for sex, cohort, and genetic relatedness. We successfully replicated (p=0.015) St6galnac1 - Paraprevotella association. These findings support the robustness of the St6galnac1 - Paraprevotella association across different sampling strategies and experimental conditions.
ER -