Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity

ABSTRACT The incidence of metabolic syndrome continues to rise globally. In mice, intravenous administration of interleukin-22 (IL-22) ameliorates various disease phenotypes associated with diet-induced metabolic syndrome. In patients, oral treatment is favored over intravenous treatment, but method...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jee-Hwan Oh, Kathryn L. Schueler, Donnie S. Stapleton, Laura M. Alexander, Chi-Liang Eric Yen, Mark P. Keller, Alan D. Attie, Jan-Peter van Pijkeren
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	diet-induced metabolic syndrome fatty liver disease IL-22 Lactobacillus reuteri probiotic engineered probiotic Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0f213e589b174cc3ad9814872f2e3b93
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0f213e589b174cc3ad9814872f2e3b93
record_format	dspace
spelling	oai:doaj.org-article:0f213e589b174cc3ad9814872f2e3b932021-11-15T15:30:15ZSecretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity10.1128/mSphere.00183-202379-5042https://doaj.org/article/0f213e589b174cc3ad9814872f2e3b932020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00183-20https://doaj.org/toc/2379-5042ABSTRACT The incidence of metabolic syndrome continues to rise globally. In mice, intravenous administration of interleukin-22 (IL-22) ameliorates various disease phenotypes associated with diet-induced metabolic syndrome. In patients, oral treatment is favored over intravenous treatment, but methodologies to deliver IL-22 via the oral route are nonexistent. The goal of this study was to assess to what extent engineered Lactobacillus reuteri secreting IL-22 could ameliorate nonalcoholic fatty liver disease. We used a mouse model of diet-induced obesity and assessed various markers of metabolic syndrome following treatment with L. reuteri and a recombinant derivative. Mice that received an 8-week treatment of wild-type probiotic gained less weight and had a smaller fat pad than the control group, but these phenotypes were not further enhanced by recombinant L. reuteri. However, L. reuteri secreting IL-22 significantly reduced liver weight and triglycerides at levels that exceeded those of the probiotic wild-type treatment group. Our findings are interesting in light of the observed phenotypes associated with reduced nonalcoholic liver disease, in humans the most prevalent chronic liver disease, following treatment of a next-generation probiotic that is administered orally. Once biological and environmental containment strategies are in place, therapeutic applications of recombinant Lactobacillus reuteri are on the horizon. IMPORTANCE In humans, nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease due to the increased prevalence of obesity. While treatment of NAFLD is often geared toward lifestyle changes, such as diet and exercise, the use of dietary supplements such as probiotics is underinvestigated. Here, we report that probiotic Lactobacillus reuteri reduces fatty liver in a mouse model of diet-induced obesity. This phenotype was further enhanced upon delivery of recombinant interleukin-22 by engineered Lactobacillus reuteri. These observations pave the road to a better understanding of probiotic mechanisms driving the reduction of diet-induced steatosis and to development of next-generation probiotics for use in the clinic. Ultimately, these studies may lead to rational selection of (engineered) probiotics to ameliorate fatty liver disease.Jee-Hwan OhKathryn L. SchuelerDonnie S. StapletonLaura M. AlexanderChi-Liang Eric YenMark P. KellerAlan D. AttieJan-Peter van PijkerenAmerican Society for Microbiologyarticlediet-induced metabolic syndromefatty liver diseaseIL-22Lactobacillus reuteriprobioticengineered probioticMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	diet-induced metabolic syndrome fatty liver disease IL-22 Lactobacillus reuteri probiotic engineered probiotic Microbiology QR1-502
spellingShingle	diet-induced metabolic syndrome fatty liver disease IL-22 Lactobacillus reuteri probiotic engineered probiotic Microbiology QR1-502 Jee-Hwan Oh Kathryn L. Schueler Donnie S. Stapleton Laura M. Alexander Chi-Liang Eric Yen Mark P. Keller Alan D. Attie Jan-Peter van Pijkeren Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity
description	ABSTRACT The incidence of metabolic syndrome continues to rise globally. In mice, intravenous administration of interleukin-22 (IL-22) ameliorates various disease phenotypes associated with diet-induced metabolic syndrome. In patients, oral treatment is favored over intravenous treatment, but methodologies to deliver IL-22 via the oral route are nonexistent. The goal of this study was to assess to what extent engineered Lactobacillus reuteri secreting IL-22 could ameliorate nonalcoholic fatty liver disease. We used a mouse model of diet-induced obesity and assessed various markers of metabolic syndrome following treatment with L. reuteri and a recombinant derivative. Mice that received an 8-week treatment of wild-type probiotic gained less weight and had a smaller fat pad than the control group, but these phenotypes were not further enhanced by recombinant L. reuteri. However, L. reuteri secreting IL-22 significantly reduced liver weight and triglycerides at levels that exceeded those of the probiotic wild-type treatment group. Our findings are interesting in light of the observed phenotypes associated with reduced nonalcoholic liver disease, in humans the most prevalent chronic liver disease, following treatment of a next-generation probiotic that is administered orally. Once biological and environmental containment strategies are in place, therapeutic applications of recombinant Lactobacillus reuteri are on the horizon. IMPORTANCE In humans, nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease due to the increased prevalence of obesity. While treatment of NAFLD is often geared toward lifestyle changes, such as diet and exercise, the use of dietary supplements such as probiotics is underinvestigated. Here, we report that probiotic Lactobacillus reuteri reduces fatty liver in a mouse model of diet-induced obesity. This phenotype was further enhanced upon delivery of recombinant interleukin-22 by engineered Lactobacillus reuteri. These observations pave the road to a better understanding of probiotic mechanisms driving the reduction of diet-induced steatosis and to development of next-generation probiotics for use in the clinic. Ultimately, these studies may lead to rational selection of (engineered) probiotics to ameliorate fatty liver disease.
format	article
author	Jee-Hwan Oh Kathryn L. Schueler Donnie S. Stapleton Laura M. Alexander Chi-Liang Eric Yen Mark P. Keller Alan D. Attie Jan-Peter van Pijkeren
author_facet	Jee-Hwan Oh Kathryn L. Schueler Donnie S. Stapleton Laura M. Alexander Chi-Liang Eric Yen Mark P. Keller Alan D. Attie Jan-Peter van Pijkeren
author_sort	Jee-Hwan Oh
title	Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity
title_short	Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity
title_full	Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity
title_fullStr	Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity
title_full_unstemmed	Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity
title_sort	secretion of recombinant interleukin-22 by engineered <named-content content-type="genus-species">lactobacillus reuteri</named-content> reduces fatty liver disease in a mouse model of diet-induced obesity
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/0f213e589b174cc3ad9814872f2e3b93
work_keys_str_mv	AT jeehwanoh secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity AT kathrynlschueler secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity AT donniesstapleton secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity AT lauramalexander secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity AT chiliangericyen secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity AT markpkeller secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity AT alandattie secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity AT janpetervanpijkeren secretionofrecombinantinterleukin22byengineerednamedcontentcontenttypegenusspecieslactobacillusreuterinamedcontentreducesfattyliverdiseaseinamousemodelofdietinducedobesity
_version_	1718427869350199296

Secretion of Recombinant Interleukin-22 by Engineered <named-content content-type="genus-species">Lactobacillus reuteri</named-content> Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity

Ejemplares similares