Biology subjects

Donohoe, D. R.

Publications and source records attributed to Donohoe, D. R..

4 recordsLinked to original sources

bioRxiv2026

Requirement of hypoxia-inducible factor 1 alpha for interleukin 1 beta induced glycolysis in colorectal cancer cells

Colorectal cancer cells increase glycolysis to help meet the metabolic demands required for cell growth. Many factors, both endogenous and exogenous, likely drive cellular metabolism and enhance glycolytic flux in colorectal cells. Interleukin-1 beta (IL-1{beta}) is a pro-inflammatory cytokine that is elevated in colorectal cancer. In this study, we investigated the effect of IL-1{beta} toward driving the cancer cell to increase glycolysis, while also suppressing the oxidation of the fiber-derived nutrient butyrate. The results presented here demonstrate that IL-1{beta} stimulated glycolysis and inhibited maximal mitochondrial respiration. IL-1{beta} also increased the phosphorylation of AKT and hypoxia-inducible factor 1 alpha (HIF1) levels. Utilizing colorectal cancer cells with AKT1/2 or HIF1 knocked out showed the requirement of these proteins in mediating the increase in glycolysis following IL-1{beta} treatment. Importantly, AKT1/2 was identified as upstream of HIF1, as IL-1{beta} still increased phosphorylation of AKT even in the absence of HIF1. However, loss of AKT1/2 completely abolished the ability of IL-1{beta} to increase HIF1 protein levels. Tumor necrosis factor alpha (TNF), another cytokine found to be elevated in colorectal cancer, also increased glycolysis in an AKT and HIF1-dependent manner. Our data point to a common pathway through AKT activation and HIF1 upregulation, by which pro-inflammatory cytokines increase glycolysis in colorectal cancer cells to help promote cancer progression.

cell biology↗

bioRxiv2026

Inflammation is the Driver of Butyrate-Producing Bacteria Change in Interleukin10 Knockout Mice

BackgroundAlterations of gut microbiota have been implicated in the development of inflammatory bowel disease. Specifically, patients with IBD show the reduced levels of gut bacteria to produce butyrate, a crucial metabolite for maintaining gut homeostasis, along with decreased levels of fecal butyrate. However, there is limited research on changes in butyrate-producing bacteria at various taxonomic levels during the development of inflammatory bowel disease. ResultsWe investigated the changes of butyrate-producing bacteria in interleukin10 knockout mice, a suitable IBD model, as these mice require gut microbiota to develop spontaneous chronic colitis. Our findings indicate increased inflammation and a metabolic shift from butyrate oxidation toward glycolysis in 9-week-old interleukin10 knockout mice. Furthermore, we observed significant changes in two terminal enzymes involved in butyrate production: a significant increase of butyrate kinase and a significant decrease of butyryl-CoA:acetate-CoA-transferase. These observations align with an increased abundance of Coprococcus comes, which utilizes butyrate kinase, and a decreased abundance of Faecalibacterium prausnitzii that utilizes butyryl-CoA:acetate-CoA-transferase. Moreover, reduced levels of acetate, a necessary co-substrate for butyryl-CoA:acetate-CoA-transferase activity, were observed in interleukin10 knockout mice. ConclusionsThese findings enhance our understanding of changes in butyrate-producing bacteria populations at various taxonomic levels, ranging from phylum to gene level in 9-week-old interleukin10 knockout mice. Furthermore, these data suggest a potential for diagnosing IBD at an early stage by analyzing the composition of butyrate-producing bacteria.

microbiology↗

bioRxiv2022

Campylobacter jejuni induces differentiation of human neutrophils to the CD16hi/CD62Llo subtype which possess cancer promoting activities

The discovery of neutrophil subtypes has expanded what is known about neutrophil functions, yet there is still much to learn about the role of these subtypes during bacterial infection. We investigated whether Campylobacter jejuni induced differentiation of human neutrophils into the hypersegmented, CD16hi/CD62Llo subtype. In addition, we investigated whether C. jejuni-dependent differentiation of this neutrophil subtype induced cancer promoting activities of human T cells and colonocytes, which were observed in other studies of hypersegmented, CD16hi/CD62Llo neutrophils. We found that C. jejuni causes a significant shift in human neutrophil populations to the hypersegmented, CD16hi/CD62Llo subtype and that those populations exhibit delayed apoptosis, elevated arginase-1 expression, and increased reactive oxygen species production. Furthermore, incubation of C. jejuni-infected neutrophils with human T cells resulted in decreased expression of the {zeta}-chain of the T cell receptor (TCR{zeta}), which was restored upon supplementation with exogenous L-arginine. In addition, incubation of C. jejuni-infected neutrophils with human colonocytes resulted in increased HIF-1 stabilization and NF-{kappa}B activation in those colonocytes, which may result in the upregulation of pro-tumorigenic genes. This response, coupled with the ability of C. jejuni-infected neutrophils to suppress TCR{zeta} expression in T cells, could result in the promotion of colorectal tumorigenesis during infection with C. jejuni.

microbiology↗

bioRxiv2019

Rumen Bacteria and Serum Metabolites Predictive of Feed Efficiency Phenotypes in Beef Cattle

The rumen microbiome is critical in ruminant nutrition and contributes to nutrient utilization and feed efficiency in cattle. Therefore, the objective of this study was to interrogate microbial and biochemical factors affecting divergences in feed efficiency in Angus steers using 16S amplicon sequencing and untargeted metabolomics. Average residual feed intake (RFI) was calculated, and steers were divided into low- and high-RFI groups. Features were ranked in relation to RFI through supervised machine learning on microbial and metabolite compositions. Residual feed intake was associated with several attributes of the rumen bacterial community. Low-RFI steers were associated with decreased bacterial - (P=0.03) and {beta}-diversity (P<0.001). Several serum metabolites were associated with RFI. Based on fold change (high/low RFI), low-RFI steers had greater abundances of pantothenate (P=0.02). Machine learning on RFI was predictive of both serum metabolomic signature and rumen bacterial composition (AUC [≥]0.7). Log-ratio proportions of the bacterial classes Flavobacteriia over Fusobacteriia were enriched in low-RFI steers (F=6.8, P=.01). Greater proportions of pantothenate-producing bacteria, such as Flavobacteriia, and/or reductions in Fusobacteriia may result in improved nutrient utilization in low-RFI steers. Pantothenate and Flavobacteriia may serve as potentially novel biomarkers to assess or predict feed efficiency in Angus steers.

microbiology↗