Helminth-Based Product and the Microbiome of Mice with Lupus

ABSTRACT The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several succ...

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Autores principales:	Hadar Neuman, Hadar Mor, Tomer Bashi, Or Givol, Abdulla Watad, Asaf Shemer, Alexander Volkov, Iris Barshack, Mati Fridkin, Miri Blank, Yehuda Shoenfeld, Omry Koren
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	helminth lupus microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d59cf3085af04671b14056e5a2b00d22
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spelling	oai:doaj.org-article:d59cf3085af04671b14056e5a2b00d222021-12-02T18:15:45ZHelminth-Based Product and the Microbiome of Mice with Lupus10.1128/mSystems.00160-182379-5077https://doaj.org/article/d59cf3085af04671b14056e5a2b00d222019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00160-18https://doaj.org/toc/2379-5077ABSTRACT The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of Akkermansia and increased abundance of several genera, including Turicibacter, Bifidobacterium, unclassified Mogibacteriaceae, unclassified Clostridiaceae, Adlercreutzia, Allobaculum, and Anaeroplasma. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus. IMPORTANCE Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following tuftsin and phosphorylcholine treatment.Hadar NeumanHadar MorTomer BashiOr GivolAbdulla WatadAsaf ShemerAlexander VolkovIris BarshackMati FridkinMiri BlankYehuda ShoenfeldOmry KorenAmerican Society for MicrobiologyarticlehelminthlupusmicrobiomeMicrobiologyQR1-502ENmSystems, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	helminth lupus microbiome Microbiology QR1-502
spellingShingle	helminth lupus microbiome Microbiology QR1-502 Hadar Neuman Hadar Mor Tomer Bashi Or Givol Abdulla Watad Asaf Shemer Alexander Volkov Iris Barshack Mati Fridkin Miri Blank Yehuda Shoenfeld Omry Koren Helminth-Based Product and the Microbiome of Mice with Lupus
description	ABSTRACT The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of Akkermansia and increased abundance of several genera, including Turicibacter, Bifidobacterium, unclassified Mogibacteriaceae, unclassified Clostridiaceae, Adlercreutzia, Allobaculum, and Anaeroplasma. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus. IMPORTANCE Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following tuftsin and phosphorylcholine treatment.
format	article
author	Hadar Neuman Hadar Mor Tomer Bashi Or Givol Abdulla Watad Asaf Shemer Alexander Volkov Iris Barshack Mati Fridkin Miri Blank Yehuda Shoenfeld Omry Koren
author_facet	Hadar Neuman Hadar Mor Tomer Bashi Or Givol Abdulla Watad Asaf Shemer Alexander Volkov Iris Barshack Mati Fridkin Miri Blank Yehuda Shoenfeld Omry Koren
author_sort	Hadar Neuman
title	Helminth-Based Product and the Microbiome of Mice with Lupus
title_short	Helminth-Based Product and the Microbiome of Mice with Lupus
title_full	Helminth-Based Product and the Microbiome of Mice with Lupus
title_fullStr	Helminth-Based Product and the Microbiome of Mice with Lupus
title_full_unstemmed	Helminth-Based Product and the Microbiome of Mice with Lupus
title_sort	helminth-based product and the microbiome of mice with lupus
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/d59cf3085af04671b14056e5a2b00d22
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Helminth-Based Product and the Microbiome of Mice with Lupus

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