Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
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- Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
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Colitis is characterized by colonic inflammation and impaired gut health. Both features aggravate obesity and insulin resistance. Host defense peptides (HDPs) are key regulators of gut homeostasis and generally malfunctioning in above-mentioned conditions. We aimed here to improve bowel function in diet-induced obesity and chemically induced colitis through daily oral administration of lysozyme, a well-characterized HDP, derived from Acremonium alcalophilum. C57BL6/J mice were fed either low-fat reference diet or HFD ± daily gavage of lysozyme for 12 weeks, followed by metabolic assessment and evaluation of colonic microbiota encroachment. To further evaluate the efficacy of intestinal inflammation, we next supplemented chow-fed BALB/c mice with lysozyme during Dextran Sulfate Sodium (DSS)-induced colitis in either conventional or microbiota-depleted mice. We assessed longitudinal microbiome alterations by 16S amplicon sequencing in both models. Lysozyme dose-dependently alleviated intestinal inflammation in DSS-challenged mice and further protected against HFD-induced microbiota encroachment and fasting hyperinsulinemia. Observed improvements of intestinal health relied on a complex gut flora, with the observation that microbiota depletion abrogated lysozyme’s capacity to mitigate DSS-induced colitis. Akkermansia muciniphila associated with impaired gut health in both models, a trajectory that was mitigated by lysozyme administration. In agreement with this notion, PICRUSt2 analysis revealed specific pathways consistently affected by lysozyme administration, independent of vivarium, disease model and mouse strain. Taking together, lysozyme leveraged the gut microbiota to curb DSS-induced inflammation, alleviated HFD-induced gastrointestinal disturbances and lowered fasting insulin levels in obese mice. Collectively, these data present A. alcalophilum-derived lysozyme as a promising candidate to enhance gut health.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 1988836 |
| Tidsskrift | Gut Microbes |
| Vol/bind | 13 |
| Udgave nummer | 1 |
| Antal sider | 20 |
| ISSN | 1949-0976 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
This work was primarily funded by Novozymes A/S, Denmark. BAHJ was supported by Lundbeck Foundation (grant number: R232-2016-2425) and Novo Nordisk Foundation (grant number: NNF17OC0026698), the latter which also supported parts of the experimental costs. The work was also partly funded by the Canadian Institutes for Health Research (CIHR) to AM (FDN-143247). BSYC was funded by doctoral scholarships from the NSERC and the Sentinel North program from the Canada First Research Excellence Fund. TS and CS were supported by the German research society DFG/IRTG 1911 Project. CS is endowed chair of Nutritional Medicine supported by Fresenius Kabi. BC?s laboratory is supported by a Starting Grant from the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation programme (grant agreement No. ERC-2018-StG- 804135), a Chaire d?Excellence from IdEx Universit? de Paris - ANR-18-IDEX-0001, an Innovator Award from the Kenneth Rainin Foundation and the national program ?Microbiote? from INSERM;H2020 European Research Council [2018-StG- 804135];Kenneth Rainin Foundation [Innovator Award];Lundbeck Foundation [R232-2016-2425];Novo Nordisk Foundation [NNF17OC0026698];Fresenius Kabi;Chaire d?Excellence from IdEx Universit? de Paris [ANR-18-IDEX-0001];Canadian Institutes for Health Research [FDN-143247];German research society [DFG/IRTG 1911 Project];Sentinel North;NSERC;German research society [DFG/IRTG 1911 Project]; We thank Joanie Dupont-Morissette, Christine Dallaire, Jenny Rancourt-Mercier, and Jacinthe Julien at IUCPQ for excellent technical assistance during animal studies. The authors thank the Hist?IM platform (INSERM U1016, Paris, France) for their help with histology. Additionally, we thank Jeanett Christiansen employed at Novozymes A/S for conducting activity assays.
Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
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