Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.04.23.590846

Association of diet and inflammation with the vaginal microbiota of pregnant individuals with or without IBD

Abstract

Background and aimsVaginal dysbiosis has been associated with adverse pregnancy outcomes. Here, we characterized the vaginal microbiota of pregnant individuals with inflammatory bowel disease (IBD) and investigated whether gut or vaginal inflammation and diet influence the vaginal microbiota diversity of these individuals. Study DesignWe recruited 48 individuals in their third trimester of pregnancy (IBD=23 and HC=18). We characterized the vaginal microbiota by 16S rRNA sequencing and the gut microbiota by shotgun sequencing. We measured fecal calprotectin in stool and pro-inflammatory cytokines in vaginal fluids. We determine dietary quality using validated 24-hour dietary recalls. ResultsPregnant individuals with IBD exhibit higher levels of fecal calprotectin and increased expression of Th17 pro-inflammatory cytokines (i.e., IL-6, IL-8, IL-17) in the vaginal mucosa compared to healthy pregnant individuals. High fecal calprotectin correlated with high vaginal microbiota diversity. Also, IL-4 (reduced in IBD) was associated with vaginal microbial composition. Regardless of IBD status, pregnant individuals with healthier diets and particularly optimal servings of vegetables and sugars exhibited a vaginal microbiota dominated by Lactobacillus crispatus, a species associated with a lower risk of preterm birth and bacterial vaginosis. ConclusionBesides gut inflammation, pregnant individuals with IBD also exhibit a Th17 immune tone in the vaginal mucosa. The vaginal microbiota diversity or composition, particularly high in the beneficial L. crispatus, is positively associated with healthier diets, regardless of IBD status. Why was the study conducted?An altered vaginal microbiota has been implicated in preterm birth. There is no research on the vaginal microbiome and the factors that influence it in pregnant individuals with Inflammatory Bowel Disease (IBD) at a higher risk of preterm delivery. Key findingsPregnant individuals with IBD exhibit a comparable vaginal microbiome to healthy pregnant individuals. However, pregnant individuals with IBD present a vaginal immune profile characterized by increased levels of Th17 pro-inflammatory cytokines. High dietary quality, and optimal consumption of vegetables and added sugars were associated with vaginal dominance by the beneficial L. crispatus. What does this add to what is known?Our results indicate that the vaginal immune environment and not the microbiome might explain poor pregnancy outcomes for individuals with IBD. Moreover, our study supports the importance of diet to favor L. crispatus, a bacterium associated with a lower risk of preterm birth.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Vargas Robles, D., Yan Rou, Y., Singha, B., Tien, J., Purandare, M., Rojas-Correa, M., Madziar, C., Picker, M., Dumont, T., Leftwich, H., Frisard, C. F., Ward, D. V., Peter, I., Olendzki, B., Maldonado-Contreras, A.. 2024-04-24. Association of diet and inflammation with the vaginal microbiota of pregnant individuals with or without IBD. https://doi.org/10.1101/2024.04.23.590846

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

KEEP EXPLORING

Related preprints

Extreme temperature exposure has negative demographic consequences for Sulfolobus acidocaldarius

Microorganisms inhabiting geothermal springs and volcanic systems experience fluctuating temperatures that can periodically exceed their upper thermal limits, but the demographic consequences of such exposure remain poorly understood. Here, we investigated demographic responses of the thermophilic archaeon Sulfolobus acidocaldarius to an extreme temperature (94.1{degrees}C) under two regimes: sustained exposure varying in duration, and episodic exposure interspersed with recovery at a permissive temperature (75{degrees}C). Under sustained exposure, populations showed no detectable loss of viability after 15 min but declined thereafter, decreasing by approximately five orders of magnitude after 120 min. Under episodic exposure, populations remained viable across nine exposure-recovery cycles but declined in density with successive cycles. Similar responses were observed for three strains, including a DNA mismatch repair knockout ({Delta}nucS), indicating that mismatch repair deficiency did not affect viability or recovery. Together, these results demonstrate that S. acidocaldarius can withstand brief and repeated exposure to near-boiling temperatures, with mortality determined primarily by cumulative exposure duration rather than a fixed thermal threshold.

microbiology↗

Bacteriophage and Antibiotic Resistance Are Positively Associated across a Phylogenetically Diverse Set of Clinical Pseudomonas aeruginosa Isolates

Co-administration of phages and antibiotics has been proposed as a therapeutic approach against antibiotic-resistant bacteria. The relationship, however, between antibiotic resistance and phage resistance in clinical isolates is unclear. Here, we examine associations between phage and antibiotic resistance profiles across a panel of Pseudomonas aeruginosa clinical isolates from the Centers for Disease Control (CDC) and Food and Drug Administration (FDA) Antimicrobial Resistance Isolate (ARI) Bank comprising 55 clinical strains with full genome sequences and antibiotic susceptibility testing (AST) data for 11 clinically relevant antibiotics. As phages in this study, we use three well-characterized, morphologically distinct phages, OMKO1, Luz19, and PAML31-1. We screen for phage resistance using a growth suppression assay, then conduct statistical analysis against antibiotic MIC (Minimum Inhibitory Concentration) data provided by the CDC to define association patterns across this dataset. We find multiple significant susceptibility correlations between pairs of antibiotics and phages, and a positive overall association between average phage resistance and antibiotic resistance across the 55 strains, even controlling for phylogenetic associations (=0.358, p<0.005). We conclude that phage and antibiotic resistance are positively associated across this clinical isolate collection, suggesting that the two resistance phenotypes are not independent in P. aeruginosa. These findings have implications for the development of phage-antibiotic cocktails.

microbiology↗

The Estuary Effect: Variations in Temperature and Salinity Alter msh Promoter Activity in Vibrio cholerae

Vibrio cholerae, the facultative pathogen underlying cholera, naturally inhabits warm aquatic estuaries. Environmental persistence is enhanced by the ability of V. cholerae to colonize host reservoirs and form multicellular biofilms, causing seasonally endemic outbreaks in many tropical regions. Most toxigenic strains utilize the type IVa mannose-sensitive hemagglutinin (MSHA) pilus for host reservoir colonization and biofilm formation. Temperature and salinity can alter V. cholerae biofilm formation, yet their impact on MSHA production specifically remains largely unknown. Here, we utilized transcriptional reporters of predicted msh promoters (msh-P1/msh-P2/msh-P3) and functional assays, to determine temperature and salinity impacts on msh expression and pilus biogenesis. Under standard laboratory conditions (30{degrees}C, 1% NaCl) only msh-P1/P2 are active and inversely-coordinated with one another. Both msh-P1/P2 activity were elevated by high temperature (37{degrees}C) and low salinity (0.25%/0.5% NaCl), and reduced by low temperature (20{degrees}C/25{degrees}C) and high salinity (2%/3% NaCl). Temperature-mediated alterations in promoter activity were not immediately reflected in changes to cell-surface MSHA levels, whereas high salinity led to decreased MSHA production. Combining high temperature (37{degrees}C) and high salinity (2%/3% NaCl), attenuated the salinity-mediated reduction of msh-P1/P2 activity. Biofilm biomass levels were only substantially heightened at 25{degrees}C and 20{degrees}C, likely a result of no temperature-dependent changes in cell-surface MSHA, and additional temperature-controlled biofilm regulation previously described. We also found msh-P1/P2 promoter activity and MSHA production varies widely across toxigenic O1 and O139 serogroups despite complete sequence homology. These results shed new light on how key signals regulate MSHA pilus production to support V. cholerae persistence in aquatic environments.

microbiology↗