Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2021.11.02.467036

The role of the gut microbiota in the effects of early-life stress and dietary fatty acids on later-life central and metabolic outcomes in mice

Reemst, K.·Tims, S.·Yam, K.-y.·Mischke, M.·Knol, J.·Brul, S.·Schipper, L.·Korosi, A.
View original source ↗Export metadata ↓

Abstract

Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We have previously shown that dietary low {omega}-6/{omega}-3 polyunsaturated fatty acid (PUFA) ratio is able to protect against ELS-induced cognitive impairments. Due to the importance of the gut microbiota as determinants of long-term health, we here study the impact of ELS and dietary PUFAs on the gut microbiota, and how this relates to the previously described cognitive, metabolic and fatty acid profiles. Male mice were exposed to ELS via the limited bedding and nesting paradigm (postnatal day (P)2 - P9) and to an early diet (P2 - P42) with either high (15) or low (1) {omega}-6 linoleic acid to {omega}-3 alpha-linolenic acid ratio. 16S ribosomal RNA was sequenced and analyzed from fecal samples at P21, P42 and P180. ELS increased {beta}-diversity at P42, which persisted into adulthood. The low {omega}-6/{omega}-3 diet prevented the ELS-induced increase in {beta}-diversity, at P42. At the level of taxa abundance, for example, the abundance of the phyla Bacteroidetes increased while Actinobacteria and Verrucomicrobia decreased with age; ELS reduced the relative abundance of the genera RC9 gut group and Rikenella into adulthood and the low {omega}-6/{omega}-3 diet reduced the abundance of the Firmicutes Erysipelotrichia. At P42, species abundance correlated with body fat mass and circulating leptin (e.g. Bacteroidetes and Proteobacteria taxa) and fatty acid profiles (e.g. Firmicutes taxa). This study gives novel insights into the impact of age, ELS and dietary PUFAs on microbiota composition, providing potential targets for non-invasive (nutritional) modulation of the ELS-induced deficits. ImportanceEarly-life stress (ELS) leads to increased vulnerability to develop mental and metabolic disorders, however the biological mechanisms leading to such programming are not fully clear. Increased attention has been given to the importance of the gut microbiota as determinant of long term health and as potential target for non-invasive nutritional strategies to protect against the negative impact of ELS. Here we give novel insights in the complex interaction between ELS, early dietary {omega}-3 availability and the gut microbiota across ages and provides new potential targets for (nutritional) modulation of the long-term effects of the early-life environment via the microbiota.

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Reemst, K., Tims, S., Yam, K.-y., Mischke, M., Knol, J., Brul, S., Schipper, L., Korosi, A.. 2021-11-03. The role of the gut microbiota in the effects of early-life stress and dietary fatty acids on later-life central and metabolic outcomes in mice. https://doi.org/10.1101/2021.11.02.467036

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

KEEP EXPLORING

Related preprints

bioRxiv2026

A conserved cysteine-histidine-glutamate metal site identifies DUF501 (Rv1025), an essential uncharacterised protein family of Mycobacterium tuberculosis, as a candidate metalloenzyme and drug target

A substantial fraction of the Mycobacterium tuberculosis proteome remains functionally uncharacterised. Rv1025, a 155-residue protein carrying the domain of unknown function DUF501 (Pfam PF04417), is essential by transposon mutagenesis and vulnerable by CRISPR interference, an attractive but neglected drug target, yet has never been functionally described. The family (4,370 proteins, no Gene Ontology term, no solved structure) is uncharacterised across all organisms and essential in three Actinobacterial genera. A Foldseek search of the AlphaFold model against complete structural databases finds no significant homolog, indicating a novel fold. The operon eno-divIC-Rv1025-ppx2 is conserved across the Actinobacteria phylum, yet AlphaFold-Multimer finds no direct complex between Rv1025 and its neighbour DivIC. Instead, conservation across 8,700 homologous sequences reveals a near-invariant Cys113-His115-Glu59 cluster forming a pocket. Holo AlphaFold3 predictions with Zn, Fe and Mn confidently place a divalent metal on this triad at 2.25-2.47 A; mutating the triad relocates the metal, and an independent backbone-geometry predictor recovers the same site, confirming specificity. The triad is universal across the family: present in all 1,472 near-complete bacterial sequences of the Pfam alignment, with no non-conservative substitution among the 2,228 sequences examined, a defining feature of bacterial DUF501 rather than a mycobacterial peculiarity. We propose that DUF501 is a metal-binding protein and candidate metalloenzyme, the first functional hypothesis for this family, whose conserved, essential metal pocket is a promising drug target. As the predictions build on a conservation-defined site within a fully computational study, they are supportive rather than proof of metal occupancy and warrant experimental validation.

microbiology↗
bioRxiv2026

Mycoplasmal endosymbionts of Trichomonas vaginalis are associated with reduced risk for Chlamydia trachomatis endometrial infection in asymptomatic, coinfected, women.

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis, the most common curable non-viral sexually transmitted infection, and Chlamydia trachomatis is a bacterial pathogen that can ascend to the upper genital tract and cause pelvic inflammatory disease, infertility, and ectopic pregnancy. T. vaginalis harbors bacterial endosymbionts, including Candidatus Malacoplasma girerdii, an obligate symbiont, and Metamycoplasma hominis, which can live freely or symbiotically. In a 16S rRNA sequencing study of the cervicovaginal microbiome of women at high risk for chlamydial infection, Ca. M. girerdii abundance was one of 13 features predicting lack of chlamydial spread to the endometrium, despite no direct association between T. vaginalis infection and reduced chlamydial ascension. Investigating the relationship between these microorganisms further, we found that T. vaginalis vaginal abundance correlated positively with chlamydial burden in women whose infection was confined to the cervix, while a nonsignificant inverse relationship was seen in women with endometrial spread. Among participants with high chlamydial burden, Ca. M. girerdii was detected exclusively in women without endometrial infection. Both endosymbionts trended toward more frequent detection, and higher abundance, in coinfected women without endometrial spread, while M. hominis abundance correlated strongly with T. vaginalis burden in this group. These findings suggest that mycoplasmal endosymbionts of T. vaginalis, rather than T. vaginalis itself, are microbial factors limiting chlamydial ascension, and point to a three-way interaction between parasite, endosymbiont, and bacterial pathogen that shapes upper genital tract C. trachomatis infection risk.

microbiology↗
bioRxiv2026

Understanding the physiological alterations of Vibrio cholerae upon exposure to L-ascorbic acid

The scourge of cholera remains a major global public health threat. It affects up to 4 million people worldwide and causes tens of thousands of deaths each year. The disease is experiencing a concerning resurgence in many parts of Africa, the Middle East, and Asia. To effectively tackle cholera and circumvent rising antimicrobial resistance, targeted biological and preventive approaches, complementing traditional rehydration, are urgently needed. In this regard, our group has demonstrated the efficacy of L-ascorbic acid in controlling the growth and pathogenesis of Vibrio cholerae in vitro. The present work further provides a mechanistic elucidation of the L-ascorbic acid-mediated physiological changes in V. cholerae and also bolsters such a non-antibiotic approach to control cholera.

microbiology↗