Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis

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...

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Autores principales:	Ida Søgaard Larsen, Benjamin A. H. Jensen, Erica Bonazzi, Béatrice S. Y. Choi, Nanna Ny Kristensen, Esben Gjerløff Wedebye Schmidt, Annika Süenderhauf, Laurence Morin, Peter Bjarke Olsen, Lea Benedicte Skov Hansen, Torsten Schröder, Christian Sina, Benoît Chassaing, André Marette
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	gut health high fat diet mucus colitis insulin resistance muramidase microbiota encroachment intestinal inflammation microbiota function host defense peptides Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/42cdead9b9e64189952dce134459fe04
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spelling	oai:doaj.org-article:42cdead9b9e64189952dce134459fe042021-11-26T11:19:48ZFungal lysozyme leverages the gut microbiota to curb DSS-induced colitis1949-09761949-098410.1080/19490976.2021.1988836https://doaj.org/article/42cdead9b9e64189952dce134459fe042021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1988836https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Colitis 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.Ida Søgaard LarsenBenjamin A. H. JensenErica BonazziBéatrice S. Y. ChoiNanna Ny KristensenEsben Gjerløff Wedebye SchmidtAnnika SüenderhaufLaurence MorinPeter Bjarke OlsenLea Benedicte Skov HansenTorsten SchröderChristian SinaBenoît ChassaingAndré MaretteTaylor & Francis Grouparticlegut healthhigh fat dietmucuscolitisinsulin resistancemuramidasemicrobiota encroachmentintestinal inflammationmicrobiota functionhost defense peptidesDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gut health high fat diet mucus colitis insulin resistance muramidase microbiota encroachment intestinal inflammation microbiota function host defense peptides Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	gut health high fat diet mucus colitis insulin resistance muramidase microbiota encroachment intestinal inflammation microbiota function host defense peptides Diseases of the digestive system. Gastroenterology RC799-869 Ida Søgaard Larsen Benjamin A. H. Jensen Erica Bonazzi Béatrice S. Y. Choi Nanna Ny Kristensen Esben Gjerløff Wedebye Schmidt Annika Süenderhauf Laurence Morin Peter Bjarke Olsen Lea Benedicte Skov Hansen Torsten Schröder Christian Sina Benoît Chassaing André Marette Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
description	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.
format	article
author	Ida Søgaard Larsen Benjamin A. H. Jensen Erica Bonazzi Béatrice S. Y. Choi Nanna Ny Kristensen Esben Gjerløff Wedebye Schmidt Annika Süenderhauf Laurence Morin Peter Bjarke Olsen Lea Benedicte Skov Hansen Torsten Schröder Christian Sina Benoît Chassaing André Marette
author_facet	Ida Søgaard Larsen Benjamin A. H. Jensen Erica Bonazzi Béatrice S. Y. Choi Nanna Ny Kristensen Esben Gjerløff Wedebye Schmidt Annika Süenderhauf Laurence Morin Peter Bjarke Olsen Lea Benedicte Skov Hansen Torsten Schröder Christian Sina Benoît Chassaing André Marette
author_sort	Ida Søgaard Larsen
title	Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
title_short	Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
title_full	Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
title_fullStr	Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
title_full_unstemmed	Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
title_sort	fungal lysozyme leverages the gut microbiota to curb dss-induced colitis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/42cdead9b9e64189952dce134459fe04
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Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis

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