2. Academic Validation
  3. Loss of vitamin C biosynthesis protects from a parasitic infection

Loss of vitamin C biosynthesis protects from a parasitic infection

  • bioRxiv. 2025 Jul 26:2025.07.22.666193. doi: 10.1101/2025.07.22.666193.
Gongwen Chen 1,  Ji Hyung Jun 2,  Tobias Wijshake 2,  Yunyang Li 1,  Minwei Yuan 1 3,  Joseph Rose 3rd 2,  Shan Li 1,  Sarah Cobb 4,  Willow Serpa 4,  Yafeng Li 2,  Li Li 5,  Weina Chen 6,  James J Collins 3rd 4 7,  Jipeng Wang 1,  Michalis Agathocleous 2 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetics and Development of Complex Phenotypes, Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
  • 2 Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, USA.
  • 3 College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.
  • 4 Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, USA.
  • 5 Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX, USA.
  • 6 Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.
  • 7 Howard Hughes Medical Institute, U.S.A.
  • 8 Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.
PMID: 40777373 DOI: 10.1101/2025.07.22.666193
Abstract

The ability to synthesize essential molecules is sometimes lost in evolution. A classic example is ascorbate (Vitamin C), which is synthesized in most Animals by L-Gulonolactone Oxidase (GULO), an enzyme lost multiple independent times in animal evolution. This event is thought to be evolutionarily neutral, however, GULO-deficient Animals including humans need to obtain ascorbate from their diet and are susceptible to ascorbate deficiency and scurvy. We therefore hypothesized that this disadvantage of GULO loss is offset by physiological benefits. Here we show that ascorbate deficiency protects mice from schistosomiasis, a debilitating parasitic disease which afflicts 250 million people. Schistosoma mansoni worms required host ascorbate to produce eggs in vivo. Consequently, ascorbate-deficient mice were protected from schistosomiasis pathologies and transmission. Intermittent ascorbate deficiency protected Gulo-deficient mice from both scurvy and schistosomiasis mortality. The effects of ascorbate on Schistosome reproduction were mediated by ascorbate-dependent histone demethylation which promoted vitellocyte development in female schistosomes. We propose that vitamin deficiencies are not always detrimental but can protect Animals from pathogens which need to obtain Vitamins from their host.

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