Biology subjects

Kärkkäinen, O.

Publications and source records attributed to Kärkkäinen, O..

3 recordsLinked to original sources

bioRxiv2026

Histomonas meleagridis infection and vaccination protection in chickens -- a metabolomics study

Histomonosis, caused by Histomonas meleagridis, is a severe disease in poultry with main pathological lesions in ceca and liver, leading to significant animal suffering and economic losses, with no licensed treatments available. While cecal pathology and microbiota disruption have been documented, the metabolic consequences of infection and vaccination remain poorly understood. Here, we used untargeted LC-MS metabolomics to profile cecal tissue and luminal digesta in a controlled vaccination-challenge chicken trial (n=100, 25 birds/group), including uninfected and unvaccinated but challenged controls, together with birds vaccinated either cloacally, or orally via an edible gel following challenge, across five post-challenge timepoints. Results showed that H. meleagridis infection caused extensive, time-dependent disruption of the cecal metabolome, especially at 7-14 days post-infection (DPI). At DPI 14, 325 tissue and 359 digesta metabolites were significantly altered in unvaccinated challenged birds. Infection was associated with depletion of microbiota-related metabolites, including dicarboxylic acids, tryptophan indoles, phytochemical derivatives, bilirubin catabolites, phenolics, vitamins, and secondary bile acids, alongside accumulation of microbial substrates and fermentation products. Changes in the host-associated metabolites indicated mucosal inflammation, epithelial injury, mitochondrial and amino acid metabolic disturbance, oxidative stress, and membrane lipid remodeling. Cloacal vaccination provided greater metabolic protection than oral vaccination, with 78.3% of disrupted metabolites preserved at DPI 14, compared with 60.7% vaccination by oral gel delivery, pointing towards the importance of vaccine take. By DPI 21, cloacally vaccinated birds showed nearly complete metabolic recovery across most pathway groups, whereas gel-vaccinated birds retained broader metabolic disturbance. These findings reveal histomonosis as a disruption of the cecal host-microbiota metabolic interface and provide a metabolite-level framework for future studies of pathogenesis, vaccine development, and prevention strategies.

pharmacology and toxicology↗

bioRxiv2025

Integrative holo-omic data analysis predicts interactions across the host-microbiome axis

Understanding the interplay between host organisms and their microbiomes is central to the development of sustainable food systems. However, high dimensionality and spurious associations remain major obstacles to extracting meaningful biological insight from multi-omic host-associated microbiome data; a challenge further exacerbated when "holo-omic" analyses across the host-microbiome boundary is considered. Here, we show that a computational method designed for multi-omic analysis in eukaryotes can be leveraged to integrate and analyse five layers of holo-omic data from porcine hosts and their gut microbiomes. We collected caecal tissue and digesta samples during a feeding trial that tested the impact of microbiota-directed fibres (acetylated galactoglucomannan) at critical developmental stages. From 800,000 features including microbial and host genes, metagenome-assembled genomes, and metabolites from caecal tissue and digesta, we used multiset correlation and factor analysis to select the most relevant features for capturing coordinated patterns across omic layers. From these features, we predicted over 2,000 putative host-microbiome interactions based on co-occurrence. Some of them reflected previously known relationships between animal and microbiome features, such as microbial genes for carbohydrate metabolism being linked to glycoside abundances in host tissue. Other predicted co-occurrences included features that were not detected in single-omic analysis and offer new hypotheses of host-microbiome interactions that warrant future investigation. Hence, we showcase an application of holo-omic analysis that avoids common pitfalls in high-dimensional data analysis; identifies known interactions as a form of validation; and most importantly, predicts new leads for understanding host-microbiome symbiosis. ImportanceWhile study systems involving mammalian hosts and their microbiomes are inherently complex, multi- and holo-omic analyses promise to provide interpretable results with translational value for the animal production industry. Unfortunately, computational methods capable of this kind of integration are currently scarce, as most existing multi-omics approaches have been developed for analysis of data layers within a single multicellular organism. We propose to adapt existing multi-omic methods for holo-omics by combining feature selection and interaction inference. This two-step analysis approach addresses common challenges in data-driven studies and can be implemented with a variety of tools for feature selection and interaction modelling. Through this holistic approach, we show that both known and novel relationships across the holobiont axis can be identified in a data-driven manner, offering new targets for the continued study of host-microbiome interactions and the effect of dietary interventions on production animals.

bioinformatics↗

bioRxiv2020

Metabolomic signature of the maternal microbiota in the fetus

The maternal microbiota affects the development of the offspring by microbial metabolites translocating to the fetus. We investigated samples of placenta, fetal intestine and brain from germ-free (GF) and specific pathogen free (SPF) mouse dams by non-targeted metabolic profiling. One hundred one annotated metabolites and altogether 3680 molecular features were present in significantly different amounts in the placenta and/or fetal organs of GF and SPF mice. The concentrations of more than half of the annotated and differentially expressed metabolites were lower in the GF organs, suggesting their microbial origin or a metabolic response of the host to the presence of gut microbiota. The clearest separation was observed in the placenta. Metabolites that were detected in lower amounts in the fetal organs in the GF mice included 5-aminovaleric acid betaine, trimethylamine N-oxide, catechol-O-sulphate, hippuric and pipecolic acid. Derivatives of the amino acid tryptophan, such as kynurenine, 3-indolepropionic acid and hydroxyindoleacetic acid, were also decreased in the absence of microbiota. Several metabolites had higher levels in the GF mice. These could be precursors of microbial metabolites or indicators of host metabolic response to the absence of gut microbiota. Ninety-nine molecular features were only detected in the SPF mice, suggesting the existence of yet unidentified microbially modified metabolites that potentially influence fetal development.

microbiology↗