Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.08.06.668965

Zinc and Cobalt exposure influence Akkermansia muciniphila growth and short-chain fatty acid metabolism

Eggers, S.·Eggers, J.·Banas, M. J.·Gennings, C.·Midya, V.
View original source ↗Export metadata ↓

Abstract

Akkermansia muciniphila is a probiotic bacterium that has been proposed as a potential intervention for depression. A. muciniphila is a common mucin degrader, producing short fatty chain acids (SCFAs), including acetate, butyrate, and propionate, which can help regulate mood via the gut-brain axis. However, the interplay between A. muciniphila and other neuroactive environmental exposures is unclear. The objective of this study was to assess the effects of Zn and Co exposure, individually and together, on A. muciniphila growth and SCFA production. Minimum Inhibitory Concentration (MIC) was calculated for each metal, and sub-MIC exposure testing at high and low levels was conducted with single and combined metals. Growth curves were measured for each exposure condition, and SCFAs were measured using liquid chromatography-mass spectroscopy. Growth and SCFA production were compared between exposures and controls using paired t-tests and linear regression models. All p-values were corrected using FDR adjustments (q-values). A. muciniphila was tolerant to both metal exposures, with MICs at 750mg/L for Zn and 4,000 mg/L for Co. Growth at 24-and 48-hours was only significantly reduced upon exposure to high levels of Co, alone and in combination with Zn. Production of propionate significantly increased with high and low Zn exposures alone and in combination with low Co exposure (q-values <0.01), and significantly decreased with high Co exposure alone and in combination with Zn (q-values <0.01). Overall, A. muciniphila was metal tolerant, supporting its use as a probiotic in the presence of other neuroactive metal exposures.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Eggers, S., Eggers, J., Banas, M. J., Gennings, C., Midya, V.. 2025-08-06. Zinc and Cobalt exposure influence Akkermansia muciniphila growth and short-chain fatty acid metabolism. https://doi.org/10.1101/2025.08.06.668965

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

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗
bioRxiv2026

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗
bioRxiv2026

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗