Biology subjects

Hanhineva, K.

Publications and source records attributed to Hanhineva, K..

4 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↗

bioRxiv2024

Blood metabolomic profiling reveals new targets in the management of psychological symptoms associated with alcohol use disorder

Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits. In this study, we investigated the impact of severe AUD (sAUD), and of a three-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal. We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in post-mortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue. Our data allow to for the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets in the management of neuropsychiatric diseases such as sAUD.

neuroscience↗

bioRxiv2022

Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain and placenta

The maternal microbiota modulates fetal development, but the mechanisms of these earliest host-microbe interactions are unclear. We compared full-term fetuses from germ-free (GF) and normally colonized mouse dams by gene expression profiling and non-targeted metabolomics. The developing immune system was strongly dependent on the maternal microbial status. In the fetal intestine, critical components mediating host-microbe interactions were differentially expressed. In fetal brain and placenta, interferon and inflammatory signaling were downregulated in germ-free fetuses. Neural system development and function, translation and RNA metabolism, and regulation of energy metabolism were significantly affected at the gene expression level. These impacts were strongly associated with microbial metabolite concentrations in the fetal tissues, suggesting that they are largely, although perhaps not exclusively mediated by maternal microbial metabolites absorbed through placenta. Several aryl sulfates were among the compounds strongly associated with gene expression differences. The germ-free fetus may suffer from depletion of queuine, a bacterial hypermodified nucleobase essential for eukaryotic tRNA stability and function.

microbiology↗

bioRxiv2021

Tissue-wide metabolomics reveals wide impact of gut microbiota on mice metabolite composition

The essential role of gut microbiota in health and disease is well-recognized, but the biochemical details underling beneficial impact remain largely undefined. Dysbiosis of gut bacteria results in the alteration of certain microbial and host metabolites, and identifying these markers could enhance the early detection of certain diseases. We report LC-MS based non-targeted metabolic profiling to demonstrate a large effect of gut microbiota on mammalian tissue metabolites. It was hypothesized that gut microbiota influences the overall biochemistry of the host metabolome and this effect is tissue-specific. Thirteen different tissues from germ-free and conventional mice were selected and their metabolic differences were analyzed. Our study demonstrated a large effect of the microbiome on mammalian biochemistry at different tissue levels and resulted in significant modulation of metabolites from multiple metabolic pathway (p [≤] 0.05). A vast metabolic response of host to metabolites generated by the microbiota was observed, Hundreds of molecular features were detected exclusively in one mouse group, with the majority of these being unique to specific tissue, suggesting direct impact gut microbiota on host metabolism.

microbiology↗