Biology subjects

Klove, S.

Publications and source records attributed to Klove, S..

3 recordsLinked to original sources

bioRxiv2025

Host age at experimental Helicobacter pylori infection shapes epithelial development of mouse gastric organoids

The bacterium Helicobacter pylori colonises gastric glands, which triggers direct responses to bacterial activity and genetic modifications of the host. While most frequently asymptomatic, infection can cause stomach cancer through a stepwise sequence from chronic gastritis to carcinoma, involving induction of stem cell-like properties of epithelial cells. We tested the effect of host age at infection on epithelial development in a mouse organoid model, where mice were infected as neonates or adults, for one month. To isolate the effects of host genetic modification, gastric organoids were grown in the absence of H. pylori and sequenced and imaged. We found that H. pylori infection early in life resulted in a larger size of the derived organoids. The expression of marker genes in organoids for different cell types was dependent on host age, suggesting a decrease in pit cells and an increase in endocrine cells with age. H. pylori infection early in life accelerated this age dependent shift, and we propose that the cell type profile affects the host response to infection.

cell biology↗

bioRxiv2025

Neonatal infection with Helicobacter pylori affects stomach and colon microbiome composition and gene expression in mice

The stomach bacterium Helicobacter pylori is estimated to infect half of the worlds population, and the health implications are affected by the age at infection. Neonatal H. pylori infection of mice is a relevant model to investigate metabolic and immunological effects. We performed an explorative study at the dynamic first month of life, to compare the composition of the gastrointestinal tract microbiome and stomach gene expression of mice neonatally infected with H. pylori with that of uninfected mice. We found that H. pylori was present only in the stomach, and that H. pylori loads increase with age from one week after infection and onwards, especially after weaning. Stomach and colon microbiome composition was strikingly similar between sites at the same sampling time, but changed significantly over one week, with increased diversity at both sites. Despite that the relative abundance of H. pylori in the stomach was low and never exceeded 3%, the composition and alpha diversity of the gastrointestinal microbiome was significantly affected by infection. In a pathway enrichment analysis we found that stomach gene expression related to the extracellular matrix, muscle contraction, and metabolism was affected by infection. Expression of these key processes was, in infected mice, shifted away from that of control mice, towards that of all mice sampled the subsequent week, which we speculate represents accelerated development in infected mice.

evolutionary biology↗

bioRxiv2025

Early-life Helicobacter pylori infection worsens metabolic state in mice receiving a high-fat diet

Perturbations to early-life microbial colonization can shape immune and metabolic development, predisposing a host to obesity. We hypothesized that neonatal infection with the ancient human symbiont Helicobacter pylori exacerbates diet-induced metabolic responses and is accompanied by alterations in endocrine and inflammatory regulation. To test this, C57BL/6JRj neonatal mice were infected with H. pylori or left uninfected and, after weaning, exposed to a high-fat diet in a long-term (5-month) study of microbiome composition and a short-term (3-week) study of circulating biomarkers and microbiome composition. In the short-term intervention, infected mice showed increased visceral adiposity. Infection was associated with altered ghrelin and leptin responses across fasting conditions, accompanied by elevated MCP-1 and IL-6, particularly in males. H. pylori infection also reinforced diet-induced shifts in gastrointestinal microbiome composition. In the long-term study, there were no differences in adiposity between infected and control mice, suggesting that diet was the dominant determinant of adiposity at this stage. Together, our findings suggest that early-life H. pylori infection amplifies the initial endocrine, inflammatory, and adipose responses to a high-fat diet.

evolutionary biology↗