Biology subjects

Lehtonen, M.

Publications and source records attributed to Lehtonen, M..

4 recordsLinked to original sources

bioRxiv2025

Prebiotic xylo-oligosaccharides for alleviation of hepatic steatosis: Results from a four-month dietary intervention and determinants of response

A common complexity from increasing rates of overweight is metabolic dysfunction associated steatotic liver disease (MASLD) which can develop into more severe conditions such as fibrosis or hepatocellular carcinoma. The gut and its microbial flora interact with the liver through the gut-liver axis and supporting healthy composition and metabolism of the microbiota can benefit metabolic health. We have previously shown in animals that a xylo-oligosaccharide (XOS) prebiotic can drive beneficial gut flora and ameliorate hepatic steatosis- our current objective is to validate these results in humans. Forty-two adults (mean age 53.7, mean BMI 33.5) ingested a prebiotic dose of XOS daily for four months. Liver fat was quantified with MRI and body composition was measured. Standard clinical measurements and untargeted metabolomes were analyzed from serum. Microbiota composition, metagenome and metabolites were analyzed from fecal samples. A subgroup analysis was conducted between non-steatotic individuals, non-responders, and responders. The XOS supplementation caused decreases in detrimental amino acid degradation products (AADPs) isovalerate, isobutyrate, and phenylacetate in the gut while serum metabolome remained stable. A decrease in liver fat during the prebiotic was accompanied by a decrease in visceral fat. In a prediction analysis, this response was driven by higher initial ratio of Bacteroides to Faecalibacterium, higher fecal AADPs, and higher serum amino acids. Non-responders had metabolomic signatures of advanced steatosis, possibly impeding effects from XOS. In overweight individuals with early hepatic steatosis, XOS may correct fermentation imbalances in the gut and decrease production of harmful metabolites, which may benefit hepatic health. IMPORTANCEPre- and probiotics are emerging, yet unknown, avenues of treatment for metabolism-associated steatotic liver disease. In overweight humans, a xylo-oligosaccharide (XOS) prebiotic induced shifts in gut bacteria and their metabolites. High proteolytic activity in the gut was predictive of hepatic response to XOS, which may serve the development of personalized treatment of fatty liver.

systems biology↗

bioRxiv2024

Effects of alcohol on the transcriptome, methylome, and metabolome of in vitro gastrulating human embryonic cells

Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neurodevelopmental disorders and birth defects. To explore the effects of PAE on gastrulation, we used an in vitro model with subchronic moderate (20 mM) and severe (70 mM) ethanol exposures during the differentiation of human embryonic stem cells into germ layer cells. We analysed genome-wide gene expression (mRNA sequencing), DNA methylation (EPIC Illumina microarrays), and metabolome (non-targeted LC-MS method) of the endodermal, mesodermal, and ectodermal cells. The largest number of ethanol-induced alterations were observed in the endodermal cells, whereas the most prominent changes were seen in the ectodermal cells. Genes of the major morphogen signaling pathways involved in gastrulation and body patterning were affected by ethanol. Many of the altered genes, such as BMP4, FGF8, SIX3, and LHX2, have been previously associated with PAE and phenotypes of FASD, like defects in heart and corpus callosum development as well as holoprosencephaly. Furthermore, methionine metabolism was altered in all germ layer cells. Our findings support the early origin of alcohol-induced developmental disorders and strengthen the role of methionine cycle in the etiology of FASD.

genetics↗

bioRxiv2022

Changes in late frontal event-related potentials to self-produced foreign phonemes correlate with improvements in pronunciation

Learning to pronounce a foreign phoneme requires an individual to acquire a motor program that enables the reproduction of the new acoustic target sound. This process is largely based on the use of auditory feedback to detect pronunciation errors to adjust vocalization. While early auditory evoked neural activity underlies automatic detection and adaptation to vocalization errors, little is known about the neural correlates of acquiring novel speech targets. To investigate the neural processes that mediate the learning of foreign phoneme pronunciation, we recorded event-related potentials (ERP) when participants (N=19) pronounced native or foreign phonemes. Behavioral results indicated that the participants pronunciation of the foreign phoneme improved during the experiment. Early auditory responses (N1 and P2 waves, approx. 85-290 ms after the sound onset) revealed no differences between foreign and native phonemes. In contrast, the amplitude of the fronto-centrally distributed late slow wave (LSW, 320-440 ms) was modulated by the pronunciation of the foreign phonemes, and the effect changed during the experiment, paralleling the improvement in pronunciation. These results suggest that the LSW may reflect higher-order monitoring processes that signal successful pronunciation and help learn novel phonemes.

neuroscience↗

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↗