Giardia antagonizes beneficial functions of indigenous and therapeutic intestinal bacteria during protein deficiency

贾第鞭毛虫在蛋白质缺乏期间对抗本土和治疗性肠道细菌的有益功能

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作者:Aadra P Bhatt, Jason W Arnold, Muyiwa Awoniyi, Shan Sun, Verônica Feijoli Santiago, Deniz Coskuner, Pedro Henrique Quintela, Kenneth Walsh, Jamie Xiao, Renay Ngobeni-Nyambi, Brenna Hansen, Ajay S Gulati, Ian M Carroll, M Andrea Azcarate-Peril, Anthony A Fodor, Jonathan Swann, Luther A Bartelt4

Abstract

Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp. and an increase in Bifidobacterium spp. This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp. mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia, despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.

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