Biology subjects

Pettersen, V. K.

Publications and source records attributed to Pettersen, V. K..

4 recordsLinked to original sources

bioRxiv2025

Metabolic reprogramming of the infant gut by bifidobacteria-based probiotics drives exclusion of antibiotic-resistant pathobionts

Early-life probiotics have emerged as a promising strategy to combat the global emergency of antimicrobial resistance by enhancing gut resilience in infants. However, how exactly probiotic bacteria affect resistant opportunistic pathogens, i.e., pathobionts, remains nascent. We investigated effects of probiotic supplementation in 152 full-term, healthy Tanzanian infants, a sub-cohort of the ProRIDE trial (NCT04172012). Administration of oral probiotics during the first 4 weeks of life led to enhanced gut colonization by the probiotic Bifidobacterium species while suppressing pathobionts such as extended-spectrum {beta}-lactamase-producing Enterobacterales (ESBL-E). Integration of metagenomics with metabolomics revealed that probiotics decreased resistome load and mobilome richness at 6 weeks, with concurrent shifts in metabolome. Specifically, the intervention increased fecal lactate and pyruvate and reduced cross-feeding pathways leading to propionate and butyrate, which partly explained the reduced ESBL-E carriage. Our findings provide mechanistic insights into how probiotic-driven Bifidobacterium colonization modulates infant gut ecosystem to attenuate antimicrobial resistance in infancy.

microbiology↗

bioRxiv2025

Early-life gut microbiome and stress-axis perturbations dysregulate systemic, mucosal, and brain immunity

BackgroundEarly-life disruptions to the gut microbiome and stress-axis significantly influence the development of immune, neuroendocrine, and other physiological systems. However, the precise microbial species and pathways mediating these effects remain poorly characterized. Using a murine model, we investigated the individual and combined effects of early-life antibiotic exposure and chronic stress on gut microbiota composition, short-chain fatty acid (SCFA) production, hypothalamic-pituitary-adrenal (HPA) axis activity, and systemic, mucosal, and neuroimmune responses. ResultsBroad-spectrum antibiotic treatments severely reduced microbial diversity and SCFA concentrations, with changes persisting into adulthood. Chronic early-life stress exerted more modest but notable effects, reducing key SCFA-producing taxa and impacting microbiome metabolic output. Combined disruptions led to altered microglial active phenotype and cytokine profiles, impaired immune cell populations, and suppressed HPA axis activity. Multi-omic correlational analyses revealed strong associations between SCFAs, specific gut microbes, and immune responses, implicating SCFAs as critical mediators of gut-brain communication. Notably, antibiotic exposure exacerbated susceptibility to allergic airway inflammation, highlighting the systemic consequences of early-life microbiome disturbances. ConclusionsThese findings demonstrate that early microbial perturbations impair neuroimmune maturation, HPA axis regulation, and host resilience to inflammatory diseases. Our study underscores the importance of preserving the early-life microbiome to support long-term immune and neurodevelopmental health, offering insights into potential therapeutic interventions for mitigating the impact of early-life microbiota disruptions.

microbiology↗

bioRxiv2020

Metaproteomic Profiling of Fungal Gut Colonization in Gnotobiotic Mice

Eukaryotic microbes can modulate mammalian host health and disease states, yet the molecular contribution of gut fungi remains nascent. We previously showed that mice exclusively colonized with fungi displayed increased sensitivity to allergic airway inflammation and fecal metabolite profiles similar to germ-free mice. To gain insights into the functional changes attributed to fungal colonization, we performed quantitative proteomic analyses of feces and small intestine of four-week-old gnotobiotic mice colonized with bacteria, fungi, or both. A comparison of fecal metaproteomic profiles between the mouse groups yielded broad changes in the relative levels of bacterial (46% of 2,860) and mouse (76% from 405) proteins. Many of the detected fungal proteins (3% of 1,492) have been previously reported as part of extracellular vesicles and having immunomodulating properties. Changes in the levels of mouse proteins derived from the jejunum (4% of 1,514) were mainly driven by proteins functional in lipid metabolism and apoptosis. Using metaproteomic profiling of gnotobiotic conditions, we show that fungal colonization profoundly impacts the host gut proteome. Our results suggest that an increased abundance of certain gut fungal species in early life may impact the developing intracellular balance of epithelial and immune cells.

microbiology↗

bioRxiv2020

Protein interactions between the oral bacteria Fusobacterium nucleatum and Porphyromonas gingivalis in biofilm and planktonic culture

The opportunistic pathogens Fusobacterium nucleatum and Porphyromonas gingivalis are Gram-negative bacteria associated with oral biofilm and periodontal disease. Although liquid cultures are often the preferred cultivation method in microbiology, bacterial cells in biofilm adopt a profoundly different phenotype reflecting the close cell-to-cell contact compare to their planktonic counterparts. To investigate F. nucleatum and P. gingivalis interactions relevant in biofilm formation, we applied liquid chromatography-tandem mass spectrometry to determine the expressed proteome of F. nucleatum and P. gingivalis cells that were grown either as biofilm or in planktonic culture, and individually or together. The proteomic analyses detected 1,322 F. nucleatum and 966 P. gingivalis proteins. We statistically compared the proteins label-free quantitative (LFQ) intensities between biofilm and planktonic culture and identified significant changes (p-value [≤]0.05) in 0,4% F. nucleatum proteins, 7% P. gingivalis proteins, and more than 14% of all proteins in the dual-species model. For both species, proteins involved in vitamin B2 (riboflavin) metabolic process had significantly increased levels in the biofilm condition. In both mono- and dual-species biofilm models, P. gingivalis increased the production of proteins functional in translation, oxidation-reduction, and amino acid metabolism, when compared to planktonic cultures. However, when we compared LFQ intensities between mono- and dual-species models, over 90% of the significantly changed P. gingivalis proteins had their levels reduced in biofilm and planktonic settings of the dual-species model. Our findings suggest that the two bacteria interact with each other at the protein level and indicate that P. gingivalis reduces the production of multiple proteins because of more favourable growth conditions provided by F. nucleatum presence. The results highlight the complex interactions of bacteria contributing to oral biofilm, which need to be considered in the design of future prevention strategies.

microbiology↗