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Short-Term Cohousing of Sick with Healthy or Treated Mice Alleviates the Inflammatory Response and Liver Damage

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Abstract

Cohousing of sick with healthy or treated animals is based on the concept of sharing an intestinal ecosystem and coprophagy, the consumption of feces, which includes sharing of the microbiome and of active drug metabolites secreted in the feces or urine. To develop a model for short-term cohousing, enabling the study of the effect of sharing an ecosystem on inflammatory states. To determine the impact of cohousing of sick and healthy mice on the immune-mediated disorders, mice injected with concanavalin A (ConA) were cohoused with healthy or sick mice or with steroid-treated or untreated mice. To determine the effect of cohousing on acetaminophen (APAP)-induced liver damage, APAP-injected mice were cohoused with N-acetyl-cysteine (NAC)-treated or untreated mice. In the ConA-induced immune-mediated hepatitis model, cohousing of sick with healthy mice was associated with the alleviation of liver damage in sick animals. Similarly, a significant decrease in serum ALT was noted in ConA-injected mice kept in the same cage as ConA-injected mice treated with steroids. A trend for reduction in liver enzymes in APAP-injected mice was observed upon cohousing with NAC-treated animals. Cohousing of sick mice with healthy or treated mice ameliorated the immune-mediated inflammatory state induced by ConA and APAP. These models for liver damage can serve as biological systems for determining the effects of alterations in the ecosystem on the immune system.

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Abbreviations

ConA:

Concanavalin A

NAC:

N-Acetyl-cysteine

APAP:

Acetaminophen

IBD:

Inflammatory bowel disease

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-alpha

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

NLRP:

Nod-like receptor protein

IFNAR1:

Type I interferon receptor

TMF/ARA160:

TATA element modulatory factor

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Funding

This work was supported in part by The Roman-Epstein Liver Research Foundation.

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Authors and Affiliations

  1. Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Ein-Kerem, POB 1200, IL91120, Jerusalem, Israel

    Yehudit Shabat, Yoav Lichtenstein & Yaron Ilan

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  1. Yehudit Shabat
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  2. Yoav Lichtenstein
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Correspondence to Yaron Ilan.

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Animal experiments were carried out according to the guidelines of the Hebrew University-Hadassah Institutional Committee for the Care and Use of Laboratory Animals. The joint ethics committee (IACUC) of Hebrew University and Hadassah Medical Center approved the study protocol for animal welfare. Hebrew University is an Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)-accredited institute.

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Shabat, Y., Lichtenstein, Y. & Ilan, Y. Short-Term Cohousing of Sick with Healthy or Treated Mice Alleviates the Inflammatory Response and Liver Damage. Inflammation 44, 518–525 (2021). https://doi.org/10.1007/s10753-020-01348-0

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  • DOI: https://doi.org/10.1007/s10753-020-01348-0

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