Biology subjects

Schippers, A.

Publications and source records attributed to Schippers, A..

6 recordsLinked to original sources

bioRxiv2026

Swimming motility in the gut microbiota is diverse and increased in inflammation.

Swimming motility has long been studied as a virulence mechanism of enteric pathogens, while the resident microbiota's motility has only been inferred from proxies or explored through a few model species. This study presents a direct, functional analysis of gut bacterial motility in health and inflammation. Using phase-contrast microscopy and high-throughput 3D tracking, we quantified motile bacteria and characterized their swimming behaviours directly in diluted fresh gut content. In healthy mice, fewer than 3% of bacteria were motile along the digestive tract, and their swimming patterns were dominated not by the run-tumble behavior of model gut species but by diverse behaviours rich in reverses. In five mouse models with intestinal inflammation (spanning chemical, genetic, dietary and infectious etiologies) the motile fraction rose by at least 4-fold, correlating with elevated Lipocalin-2 where measured. Reverse-rich patterns remained prevalent in these inflamed conditions, with the notable exception of Salmonella infection. Paired metagenomics and metatranscriptomics showed enrichment of flagellar genes, while communities transferred into cecal water from inflamed mice raised their motile fraction within an hour, indicating that the rise reflects both enrichment of motile taxa and rapid modulation within existing populations. In vitro assays with human-derived isolates confirmed motility across several phyla, with variability down to strain level, and identified oxygen and viscosity as key modulators. These findings support increased motility as a hallmark of the inflamed gut and challenge established assumptions about gut bacterial motility.

microbiology↗

bioRxiv2026

Sensorimotor training lightens the perceived weight of body augmentation devices

Wearable haptic and robotic devices must transmit useful forces and tactile information without remaining perceptually intrusive. Here we show that perceived weight provides a behavioral marker of this transition toward transparency. Participants judged the weight of their hand with or without a finger-extending exoskeleton before and after object-manipulation training with either the exoskeleton or a structurally matched control device. Psychometric modelling decomposed perceived effector weight into biological-hand and artificial-device components. Attachment produced baseline attenuation of both hand and device weight, whereas training selectively increased attenuation of the finger-extending exoskeleton. Thus, active use made the augmenting device contribute less to perceived effector weight while leaving perceived hand weight stable. These findings suggest that wearable devices become perceptually lighter when their mechanical consequences are integrated into sensorimotor control. Perceived weight offers a compact metric for evaluating transparency, embodiment, and usability in wearable haptic and robotic interfaces. SummarySensorimotor training makes wearable finger-extending exoskeletons feel lighter.

neuroscience↗

bioRxiv2025

The adhesion molecules β7 integrin and L-selectin contribute to cholestatic liver disease in male mice

Background & AimsPrimary sclerosing cholangitis (PSC) is a long-term progressive disease, often occurring in conjunction with inflammatory bowel disease (IBD). Dysregulated immune cell migration and gut microbiota alterations are implicated in disease progression. Livers of PSC patients show upregulation of the endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1). Here we examined the role of the leukocytic adhesion molecules (AM) {beta}7 integrin and L-selectin, both binding partners of MAdCAM-1, in an experimental mouse model resembling aspects of human PSC. MethodsWild type (WT), {beta}7 integrin-deficient ({beta}7-/-), L-selectin-deficient (L-sel-/-), and L-selectin/{beta}7 integrin double-deficient (L-sel-/-/{beta}7-/-) male mice were compared in the model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy. The extent of pathology was evaluated by serum parameters, histology, flow cytometry, and expression of inflammatory mediators. Fecal microbiota changes were assessed by 16S rRNA amplicon sequencing and intestinal permeability was measured by FITC-dextran assay. ResultsAM-deficient mice were markedly protected from DDC-induced cholangiopathy. Hepatic immune cell populations of AM-deficient mice differed significantly from those of WT mice. Adoptively transferred {beta}7-/- CD8+ T cells caused significantly less liver damage than CD8+ WT T cells in DDC-treated {beta}7-/- mice. DDC-feeding caused substantial changes in fecal microbiota profiles, which differed between the mouse strains, and a strong increase in intestinal permeability that was significantly lower in {beta}7-/- than WT mice. Conclusions{beta}7 integrin and L-selectin contribute to DDC-induced cholangiopathy with {beta}7 integrin-expressing CD8+ T cells playing a crucial role in promoting pathogenesis. In addition, AM-expressing immune cells may contribute to the inflammatory process by causing unfavorable gut microbiota shifts and destabilizing the gut barrier. Synopsis{beta}7 integrin- and/or L-selectin-deficient mice are less susceptible to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced experimental cholangiopathy. {beta}7 integrin-expressing CD8+ T cells contribute to DDC-induced pathogenesis. {beta}7 integrin promotes DDC-induced gut barrier dysfunction and microbiota shifts, potentially exacerbating hepatic injury.

immunology↗

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↗

bioRxiv2024

CREB determines the expression of ST2 in Tregs and mediates the balance between type 1 and type 2 immune responses

Regulatory T cells (Tregs) are gatekeepers of immune homeostasis and characterized by expression of Foxp3, which maintains Treg identity. Here we demonstrate that in mice with a Foxp3-specific knockout of CREB, enhanced numbers of Tregs are found in vivo in spleen, lung and colon. These Tregs display a reduced Foxp3 expression, but enhanced expression of the IL-33 receptor (ST-2), IL-10, IL-13, and CREM. CREB deficient Tregs were highly suppressive in vitro and prevented disease activity in CD4 T cell mediated transfer colitis in an IL-10 dependent way. Mechanistically CREB fulfils dual roles in Tregs. First it downregulates Foxp3 expression, however in cooperation with CREM, CREB expression in Tregs alters chromatin accessibility to the ST-2 region and thereby influences T cell specific immune responses mediated by IL-10. Brief summary: Mice with a Foxp3-specific knockout of CREB display enhanced expression of IL-13, IL-10, ST-2 and CREM, which prevents gut inflammation GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/601312v2_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@a2d341org.highwire.dtl.DTLVardef@1db6852org.highwire.dtl.DTLVardef@19e024borg.highwire.dtl.DTLVardef@a8c84d_HPS_FORMAT_FIGEXP M_FIG C_FIG Created by Biorender

immunology↗

bioRxiv2021

Caregiving quality modulates neuroendocrine and immunological markers in young children in foster care who have experienced early adversity

BackgroundEarly adversity is believed to alter the bodys stress response systems, putting children at increased risk for somatic and mental health problems. However, it remains unclear whether such alterations normalize under improved caregiving experiences. Thus, the goal of the present study was to investigate i) whether children in foster care show endocrine and immunological alterations relative to children living with their biological families, ii) whether these alterations change over time spent with the foster family and iii) whether the alterations are modulated by current caregiving experiences. MethodsA total of 94 children in foster care and 157 biological children, aged two to seven years, took part in a longitudinal study with three assessments conducted over a 12-month study period. At the initial assessment, children lived for an average of 18 months with their current foster families. Childrens cortisol, dehydroepiandrosterone (DHEA) and progesterone concentrations and cortisol/DHEA ratios were measured in scalp hair and childrens secretory immunoglobulin A (sIgA) levels in saliva. Caregiving quality was assessed based on caregiver-reports and observational measures of caregiver-child interactions. ResultsChildren in foster care had lower cortisol/DHEA ratios and higher progesterone concentrations than biological children, while no group differences were found for cortisol, DHEA or sIgA. Time spent with the current foster family did not significantly influence the childs endocrine or immunological markers. Importantly, caregiving quality modulated cortisol/DHEA ratios and sIgA concentrations: children in foster care of lower caregiving quality had lower cortisol/DHEA ratios than children in foster care of higher caregiving quality and showed decreasing, rather than increasing, sIgA concentrations across the study period. ConclusionsOur results indicate that caregiving quality in the foster family may have an important modulating effect on selected indicators of the childs stress response and could thereby mitigate the possible consequences of early childhood adversity.

physiology↗