Biology subjects

Treichel, N. S.

Publications and source records attributed to Treichel, N. S..

5 recordsLinked to original sources

bioRxiv2026

A mixture of plant polyphenols unexpectedly aggravates liver metastasis of colorectal cancer in mice

Epidemiological studies suggest that vegetarian diets are associated with lower cancer incidence and mortality, an effect attributed in part to phytochemicals such as polyphenols and carotenoids. Although numerous in vitro experiments and investigations using immunodeficient rodent models report tumor-suppressive activities of phytochemicals, their impact on tumor progression in immunocompetent hosts remains insufficiently understood. Here, we examined the influence of a defined plant phytochemical mixture (PPM) on the growth of colon cancer liver metastases, both in vitro and in immunocompetent mice. Consistent with the prevailing literature, treatment of the murine colon cancer cell line MC38 with the PPM significantly reduced cell proliferation and survival in vitro. Strikingly, however, administration of the PPM to mice bearing MC38-derived hepatic metastases markedly accelerated tumor growth. Immunohistochemical analyses revealed a significantly increased accumulation of immune cells--specifically CD45 leukocytes and F4/80 macrophages--at the periphery of the metastatic lesions in PPM-treated animals. To assess the functional relevance of this inflammatory response, the PPM was combined with the anti-inflammatory drug prednisolone. This intervention resulted in significantly reduced metastatic burden, supporting the notion that the PPM exacerbates tumor progression through enhanced peritumoral inflammation. These findings highlight the importance of validating observations from cell culture and immunodeficient models in fully immunocompetent systems. They further emphasize that the immunomodulatory effects of plant phytochemicals warrant careful and comprehensive investigation.

cancer biology↗

bioRxiv2025

Intercellular adhesion molecule-1 protects against adipose tissue inflammation and insulin resistance but promotes liver inflammation and hepatic fibrosis in mice

Metabolic dysfunction associated steatotic liver disease (MASLD) presents a growing global health problem with a range of manifestations, including steatosis, steatohepatitis, and cirrhosis. It is strongly associated with obesity, disease progression being promoted not only by hepatic leukocyte accumulation but also by inflammatory signals from adipose tissue and an altered gut microbiome. To determine the contribution of intercellular adhesion molecule-1 (ICAM-1) to MASLD pathogenesis, mice with an ICAM-1 mutation (Icam1tmBay) were compared to wild type (WT) mice in a Western-style diet (WD) model. WD-induced MASLD was accompanied by increased ICAM-1 expression in liver, epididymal white adipose tissue (EWAT), and intestine in WT mice. WD-fed Icam1tmBay mice exhibited increased circulating neutrophils, higher frequencies of inflammatory leukocytes in EWAT, and a worsened glucose tolerance when compared to WT mice. In contrast, the mutation resulted in reduced WD-induced liver damage and less accumulation of intrahepatic leukocytes. WD-feeding caused substantial changes in fecal microbiota with decreased microbial diversity that differed between the mouse strains. In conclusion, ICAM-1 positively regulates adipose tissue homeostasis and protects from insulin resistance but promotes liver damage in diet-induced obesity. This points to various organ-specific roles for ICAM-1 and the potential of liver-specific targeting of ICAM-1 for treatment of MASLD.

immunology↗

bioRxiv2025

Function-Based Selection of Synthetic Communities Enables Mechanistic Microbiome Studies

Understanding the complex interactions between microbes and their environment requires robust model systems such as synthetic communities (SynComs). We developed a functionally directed approach to generate SynComs by selecting strains that encode key functions identified in metagenomes. This approach enables the rapid construction of SynComs tailored to any ecosystem. To optimize community design, we implemented genome-scale metabolic models, providing in silico evidence for cooperative strain coexistence prior to experimental validation. Using this strategy, we designed multiple host-specific SynComs, including those for the rumen, mouse, and human microbiomes. By weighting functions differentially enriched in diseased versus healthy individuals, we constructed SynComs that capture complex host-microbe interactions. Notably, we designed an inflammatory bowel disease SynCom of 10 members that successfully induced colitis in gnotobiotic IL10-/- mice, demonstrating the potential of this method to model disease-associated microbiomes. Our study establishes a targeted framework for designing SynComs to advance mechanistic insights into host-microbe interactions. HighlightsO_LIAutomated functional selection of SynComs based on metagenomic data C_LIO_LIEcosystem-specific SynComs capture the functional landscape of microbiota C_LIO_LIColitis-inducing SynCom developed as a model for inflammatory bowel diseases C_LI

microbiology↗

bioRxiv2025

Benchmarking of shotgun sequencing depth highlights strain-level limitations of metagenomic analysis

Shallow metagenomics promises taxonomic and functional insights into samples at an affordable price. To determine the depth of sequencing required for specific analysis, benchmarking is required using defined microbial communities. We used complex mixtures of DNA from cultured gut bacteria and analysed taxonomic composition, strain-level resolution, and functional profiles at up to eleven sequencing depths (0.1-50.0 Gb). Reference-based analysis provided accurate taxonomic, and strain-level insights at 0.5-1.0 Gb. In contrast, de-novo metagenome-assembled genome (MAG) reconstruction required deep sequencing (>10 Gb), and even high-quality MAGs were chimeric, with 54.5 to 81.8 % accurately representing the original strains, depending on the bioinformatic approach used. However, the issue of chimeric MAGs can be reduced by using strain-aware assembly methods or long-read sequencing. Functionally, 2 Gb provided reliable insights at the pathway level, but sufficient proteome coverage was only achieved at or above 10 Gb. Library preparation and host DNA contamination were identified as confounders in shallow metagenomic analysis. This comprehensive analysis using complex mock communities provides guidance to an increasing community of scientists interested in using shallow metagenomics, and highlights the limitations of MAGs in accurately capturing strain-level diversity.

microbiology↗

bioRxiv2022

A physiologically based model of bile acid metabolism in mice

Bile acid (BA) metabolism is a complex system that includes a wide variety of primary and secondary, as well as conjugated and unconjugated BAs that undergo continuous enterohepatic circulation (EHC). Alterations in both composition and dynamics of BAs have been associated with various diseases. However, a mechanistic understanding of the relationship between altered BA metabolism and related diseases is lacking. Computational modeling may support functional analyses of the physiological processes involved in the EHC of BAs along the gut-liver axis. In this study, we developed a physiologically-based model of murine BA metabolism describing synthesis, conjugation, microbial transformations, systemic distribution, excretion and EHC of BAs at the whole-body level. For model development, BA metabolism of specific pathogen-free (SPF) mice was characterized in vivo by measuring BA levels and composition in various organs, expression of transporters along the gut and cecal microbiota composition. We found significantly different BA levels between male and female mice that could only be explained by adjusted expression of the hepatic enzymes and transporters in the model. Of note, this finding was in agreement with experimental observations. The model for SPF mice could also describe equivalent experimental data in germ-free mice by specifically switching of microbial activity in the intestine. The here presented model can therefore facilitate and guide functional analyses of BA metabolism in mice, e.g., the effect of pathophysiological alterations on BA metabolism and translation of results from mouse studies to a clinically relevant context through cross-species extrapolation.

systems biology↗