Biology subjects

Yeoh, B. S.

Publications and source records attributed to Yeoh, B. S..

4 recordsLinked to original sources

bioRxiv2025

Targeting anemia-induced CD71+ reticulocytes protects mice from Plasmodium infection

Malaria, caused by Plasmodium spp., is a global health concern linked to anemia and increased mortality. Compensatory erythropoiesis seen during acute anemia results in an increased circulating reticulocyte count (i.e., immature RBC) a key factor in understanding the relationship between pre-existing anemia and Plasmodium burden. Reticulocytes in mice are marked by transferrin receptor (CD71+) and glycophorin A-associated protein (Ter119+). To model acute anemia with increased reticulocytes, C57BL/6 mice were either bled (i.e. phlebotomized) or administered phenylhydrazine, before being infected with Plasmodium yoelii (P. yoelii), a mouse-specific strain with a preference for reticulocytes. In P. yoelii-infected anemic mice, we observed heightened parasitemia and significant body weight loss compared with non-anemic P. yoelii-infected mice. Additionally, serum inflammatory cytokines, erythropoietin, and liver injury markers, along with hemozoin deposition significantly increased in anemic P. yoelii-infected mice. RBC transfusion from healthy normal donors to P. yoelii-infected anemic recipient mice ameliorated anemia by reducing overall reticulocyte count and increasing mature RBC count. RBC transfusion rescued body weight loss, decreased parasitemia, and reduced serum erythropoietin levels. Finally, to confirm the role of reticulocytes in P. yoelii infection, reticulocytes were depleted using anti-CD71 monoclonal antibody in P. yoelii-infected mice. We observed improvement in hematologic parameters and stark reduction in parasitemia in both pre-existing anemic and non-anemic P. yoelii-infected mice. Collectively, our results suggest that pre-existing anemia may increase the risk of Plasmodium infection due to the greater reticulocytes population. Anti-CD71 treatment in Plasmodium infection may offer a novel therapeutic strategy to combat Plasmodium infection and malaria. Grant supportThis work was supported by grants from the Crohns and Colitis Foundation (CCF) and American Heart Association (AHA) Career Development Award (854385 and 855256 respectively) to Piu Saha; grant from the National Institutes of Health (NIH) to Matam Vijay-Kumar (DK134053) and Liver Scholar Award from American liver Foundation to Beng San Yeoh.

pathology↗

bioRxiv2024

The ketone body β-Hydroxybutyrate mediated epigenetic chromatin β-hydroxybutyrylation protects kidneys

Starvation, intermittent fasting and exercise, all of which are recommended lifestyle modifiers share a common metabolic signature, ketogenesis to generate the ketone bodies, predominantly {beta}-hydroxybutyrate. {beta}-hydroxybutyrate exerts beneficial effects across various contexts, preventing or mitigating disease. We hypothesized that these dynamic health benefits of {beta}-hydroxybutyrate might stem from its ability to regulate genome architecture through chromatin remodeling via histone {beta}-hydroxybutyrylation, thereby influencing the transcriptome. Focusing on the kidney, which is an end organ protected by {beta}-hydroxybutyrate, we examined histone {beta}-hydroxybutyrylation-mediated chromatin remodeling. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. Significant {beta}-hydroxybutyrylation was observed in the kidneys and the most highly upregulated gene actively transcribed and translated was 3-hydroxy-3-methyglutaryl CoA Synthase 2 (Hmgcs2), a gene responsible for the biosynthesis of {beta}-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures were enriched with genes related to immune function such as protein tyrosine phosphatase receptor type C (Ptprc) and lymphocyte cytosolic protein 1 (Lcp1), which exhibited reduced transcription and translation. These results reveal that renal epigenetic histone {beta}-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly to protect kidneys and lower hypertension. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/628574v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@f16cdorg.highwire.dtl.DTLVardef@a22427org.highwire.dtl.DTLVardef@f3a6d3org.highwire.dtl.DTLVardef@4d705d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

physiology↗

bioRxiv2020

Reconstitution of the host holobiont acutely increases bone growth of the gnotobiotic rat

In recent years there has been growing evidence regarding the effect of microbiota on the skeletal growth and homeostasis. Here we present, for the first time, accelerated longitudinal and radial bone growth in young (7-week-old) germ-free male rats after short-term exposure to a newly established gut microbiota. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in tibia diaphysis. In addition, the number of small-in-size adipocytes increased, while the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats. The observed changes in bone status were paralleled with a positive shift in microbiota composition towards short chain fatty acids (SCFA)-producing microbes, which reflected a dramatic increase in cecal concentration of SCFA, specifically butyrate. Further, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels, implicating an involvement of the somatotropic axis. Increased serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase and resembled reversal of dysbiosis in adolescence, which is marked by rapid skeletal expansion. These findings may help in developing microbiota-based therapeutics to combat bone related disorders resulting from hormonal defects and/or malnutrition in children and adolescence.

physiology↗

bioRxiv2019

Bacterial Hyperswarming as a Protective Response to Intestinal Stress

Bacterial swarming, a collective movement on a surface, has rarely been associated with human pathophysiology. Here, we report for the first time that bacterial swarmers are associated with protection against intestinal inflammation. We show that bacterial swarmers are highly predictive of intestinal stress in mice and humans. We isolated a novel Enterobacter swarming strain, SM3, from mouse feces. SM3 and other known commensal swarmers contrast to their respective swarming-deficient, but swimming-competent isogenic strains abrogated intestinal inflammation in mice. Treatment of colitic mice with SM3, but not its mutants, enriched beneficial fecal anaerobes belonging to the family, Bacteroidales S24-7. We observed SM3 swarming associated pathways in the in vivo fecal metatranscriptomes. In vitro growth of S24-7 was enriched in presence of SM3 or its mutants conjecturing that bacterial swarming in vivo might influence SM3s access to S24-7 in the intestines. Overall, our work identifies a new paradigm in which intestinal stress allows for the emergence of swarming bacteria, which can counterintuitively heal intestinal inflammation.

microbiology↗