Biology subjects

Bandsma, R. H. J.

Publications and source records attributed to Bandsma, R. H. J..

5 recordsLinked to original sources

bioRxiv2025

Feeding a low-protein diet exacerbates the susceptibility to Citrobacter rodentium and Dextran Sulfate Sodium-induced intestinal injury in mice.

Globally, almost half of all early childhood deaths are linked to severe undernutrition, herein referred to as severe malnutrition. Mortality in severely malnourished children is often attributed to common infectious diseases, including enteric infections. It has been proposed that impaired intestinal barrier function contributes to mortality, but direct evidence is limited and thus there exists a need to develop improved preclinical models to test these and other mechanistic hypotheses. In this study, we aimed to describe differences in response to enteric inflammation and infection in the colon of malnourished mice compared to well-nourished littermates. C57Bl/6 male weanlings were fed isocaloric diets, either a low 1% protein diet (LPD) or a control 18% protein diet (CPD) for 2-weeks either in combination with oral administration of dextran sodium sulfate (DSS), or Citrobacter rodentium (C. rodentium). LPD-fed mice were more susceptible to DSS or C. rodentium as evidenced by increased clinical severity scores, and reaching their humane endpoints. LPD-fed mice also showed more signs of colonic dysfunction with reduced levels of tight junction proteins, higher colonic pathogen load, and increased systemic inflammation and bacterial spread. Taken together, these observations show that malnourished animals have increased susceptibility to intestinal dysfunction caused by either chemical exposure or infection. These novel preclinical models can be used to further elucidate the processes involved in enteric dysfunction in malnutrition and to test therapies to improve intestinal repair and outcomes.

microbiology↗

bioRxiv2025

Biological landscape of acute illness in children in sub-Saharan Africa and South Asia

Childhood illnesses including pneumonia, diarrhoea and malaria are leading causes of hospitalisation and mortality in resource-limited settings. However, we lack understanding of whether systemic responses to such diverse clinical syndromes are shared or specific, how they are impacted by malnutrition and how they differ from well children. We performed multi-omic profiling of plasma proteins, and serum metabolites and lipids in acutely ill hospitalised and well children in sub-Saharan Africa and South Asia. Using network-based clustering and mixed-effects modelling, we identified common and syndrome-specific omics responses to acute illness. We found that malnutrition often modifies host responses to disease. Although the internal structure of individual omics modules was largely preserved between ill and well children, the interactions between these preserved modules were markedly reorganised during acute illness. Compared to well children, biological systems in hospitalised children were more interconnected, exhibiting denser cross-omics interactions. These findings reveal widespread multisystem mobilisation during paediatric acute illness, offer deeper mechanistic insights and highlight candidate pathways for therapeutic intervention in high-burden settings.

systems biology↗

bioRxiv2023

Upregulated pexophagy limits the capacity of selective autophagy

Selective autophagy is an essential mechanism to maintain organelle integrity and cellular homeostasis through the constant recycling of damaged or superfluous components. While distinct selective autophagy pathways mediate the degradation of diverse cellular substrates including organelles and pathogens, whether these distinct pathways can influence one another remains unknown. We address this question here using pexophagy, the autophagic degradation of peroxisomes, as a model. We demonstrate in cells that upregulated pexophagy exhausts selective autophagy and limits the degradation of both mitochondria and protein aggregates. We confirmed this finding in the pexophagy-mediated form of Zellweger Spectrum Disorder, a rare disease characterized by peroxisome dysfunction. Further, we extend the generalizability of limited selective autophagy by determining that increased aggrephagy reduces pexophagy using a model of Huntingtons Disease. Our findings suggest that the degradative capacity of selective autophagy can become limited by an increased substrate load.

cell biology↗

bioRxiv2023

Age and diet modulate the insulin-sensitizing effects of exercise: a tracer-based oral glucose tolerance test

Diet modulates the development of insulin resistance during aging. This includes tissue-specific alterations in insulin signaling and mitochondrial function, which ultimately affect glucose homeostasis. Exercise stimulates glucose clearance, mitochondrial lipid oxidation and enhances insulin sensitivity. It is not well known how exercise interacts with age and diet in the development of insulin resistance. To investigate this, oral glucose tolerance tests (OGTT) with a tracer were conducted in mice ranging from 4 to 21 months of age, fed a low- (LFD) or high-fat diet (HFD), with or without life-long voluntary access to a running wheel (RW). We developed a computational model to derive glucose fluxes, which were commensurate with independent values from steady-state tracer infusions. Both insulin sensitivity indices derived for peripheral tissues and liver (IS-P and IS-L, respectively) were steeply decreased by aging and a HFD. This preceded the age-dependent decline in the mitochondrial capacity to oxidize lipids. In LFD young animals, RW access enhanced the IS-P concomitantly with the muscle {beta}-oxidation capacity. Surprisingly, RW access completely prevented the age-dependent IS-L decrease, but only in LFD animals. This study indicates, therefore, that endurance exercise can improve the age-dependent decline in organ-specific IS mostly in the context of a healthy diet.

physiology↗

bioRxiv2021

Micronutrient supplements with iron promote disruptive protozoan and fungal communities in the developing infant gut

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, adverse events resulting in gastrointestinal disorders, largely associated with iron, has resulted in ongoing debate over their administration. To better understand their impact on gut microbiota, we analysed the bacterial, protozoal, fungal and helminth communities of stool samples collected from children that had previously been recruited to a cluster randomized controlled trial of micronutrient supplementation in Pakistan. We show that while bacterial diversity was reduced in supplemented children, vitamins and iron may promote colonization with distinct protozoa and mucormycetes, whereas the addition of zinc ameliorates this effect. In addition to supplements, residence in a rural versus urban setting is an important determinant of eukaryotic composition. We suggest that the risks and benefits of such interventions may be mediated in part through eukaryotic communities, in a manner dependent on setting.

microbiology↗