Metagenomic Alterations in Gut Microbiota Precede and Predict Onset of Colitis in the IL10 Gene-Deficient Murine Model

Miyoshi, Jun; Lee, Sonny T. M.; Kennedy, Mark; Puertolas, Mora; Frith, Mary; Koval, Jason C.; Miyoshi, Sawako; Antonopoulos, Dionysios A.; Leone, Vanessa; Chang, Eugene B.

doi:10.1016/j.jcmgh.2020.08.008

Cited by 8 publications

(3 citation statements)

References 21 publications

(28 reference statements)

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“…In addition to its role in balancing gut immune reactivity, IL‐10 plays a critical role in interorgan communication (Madsen et al., 1997; Miyoshi et al., 2021; Oshima et al., 2001). The mammalian gut participates in several interorgan communications in the mammalian system (Forkosh & Ilan, 2019; Tripathi et al., 2018; Zaiss et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

Reduced estrogen signaling contributes to bone loss and cardiac dysfunction in interleukin‐10 knockout mice

Alake,

Ice,

Robinson

et al. 2024

Physiological Reports

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Characterization of the interleukin (IL)‐10 knockout (KO) mouse with chronic gut inflammation, cardiovascular dysfunction, and bone loss suggests a critical role for this cytokine in interorgan communication within the gut, bone, and cardiovascular axis. We sought to understand the role of IL‐10 in the cross‐talk between these systems. Six‐week‐old IL‐10 KO mice and their wild type (WT) counterparts were maintained on a standard rodent diet for 3 or 6 months. Gene expression of proinflammatory markers and Fgf23, serum 17β‐estradiol (E2), and cardiac protein expression were assessed. Ileal Il17a and Tnf mRNA increased while Il6 mRNA increased in the bone and heart by at least 2‐fold in IL‐10 KO mice. Bone Dmp1 and Phex mRNA were repressed at 6 months in IL‐10 KO mice, resulting in increased Fgf23 mRNA (~4‐fold) that contributed to increased fibrosis. In the IL‐10 KO mice, gut bacterial β‐glucuronidase activity and ovarian Cyp19a1 mRNA were lower (p < 0.05), consistent with reduced serum E2 and reduced cardiac pNOS3 (Ser1119) in these mice. Treatment of ileal lymphocytes with E2 reduced gut inflammation in WT but not IL‐10 KO mice. In conclusion, our data suggest that diminished estrogen and defective bone mineralization increased FGF23 which contributed to cardiac fibrosis in the IL‐10 KO mouse.

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Section: Discussionmentioning

confidence: 99%

Reduced estrogen signaling contributes to bone loss and cardiac dysfunction in interleukin‐10 knockout mice

Alake,

Ice,

Robinson

et al. 2024

Physiological Reports

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“…Highlighting the importance of microbial derived metabolites, we showed that E. rectale was also able to lower ROS levels during DSS induced colitis, while GSH alone was not sufficient in lowering ROS in inflamed cells. water with cefoperazone sodium salt (CPZ; 0.5 mg/mL), a broad spectrum antibiotic, when they were in the third week of gestation, to instill inherited dysbiosis (95). The duration of CPZ exposure lasted until pups were weaned at 21 days of age.…”

Section: Discussionmentioning

confidence: 99%

“…We conducted this experiment using two different experimental sets of mice - Control mice (Control); mice without vertically transmitted dysbiosis, and mice with inherited dysbiosis (Dysbiotic), to investigate the impact of the resilient microbial populations on inherited dysbiosis. We supplemented dams with autoclaved drinking water with cefoperazone sodium salt (CPZ; 0.5 mg/mL), a broad spectrum antibiotic, when they were in the third week of gestation, to instill inherited dysbiosis (95). The duration of CPZ exposure lasted until pups were weaned at 21 days of age.…”

Section: Methodsmentioning

confidence: 99%

Eubacterium rectaledetoxification mechanism increases resilience of the gut environment

Richie,

Wiechman,

Ingold

et al. 2024

Preprint

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Lachnospiraceae members were highly detected in dysbiotic IL-10 KO mice that displayed similar physiological outcomes as control mice. Lachnospiraceae is a highly diverse family of microbes that have been shown to display both commensal and pathogenic characteristics in the colon environment. We investigated the impact of genetic variation in five Lachnospiraceae strains on lowering cellular inflammation and ROS levels. Cell free spent media (CFSM) fromEubacterium rectaleresulted in lowered ROS, and nitric oxide levels in stressed colon cells. We demonstrated through an array of multi-omics and molecular techniques that glutathione (GSH) biosynthesized byE. rectalewas able to alleviate host ROS damage. We further showed downregulation of cell stress and immune response genes by host RNA sequencing, which is evidence thatE. rectalemicrobial products promote recovery and alleviate ROS stress.

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Ablation of CD226 on CD4+ T cells modulates asthma progress associated with altered IL-10 response and gut microbiota

Xie

Zhang

Wang

et al. 2023

International Immunopharmacology

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Metagenomic Alterations in Gut Microbiota Precede and Predict Onset of Colitis in the IL10 Gene-Deficient Murine Model

Abstract: Currently, predictive markers for the development and course of inflammatory bowel diseases (IBD) are not available. This study supports the notion that gut microbiome metagenomic profiles could be developed into a useful tool to assess risk and manage human IBD.

Cited by 8 publications

References 21 publications

Reduced estrogen signaling contributes to bone loss and cardiac dysfunction in interleukin‐10 knockout mice

Reduced estrogen signaling contributes to bone loss and cardiac dysfunction in interleukin‐10 knockout mice

Eubacterium rectaledetoxification mechanism increases resilience of the gut environment

Ablation of CD226 on CD4+ T cells modulates asthma progress associated with altered IL-10 response and gut microbiota

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