Preclinical study finds gut fungi influence neuroimmunity and behavior


Date:
February 16, 2022
Source:
Weill Cornell Medicine
Summary:
A specific group of fungi residing in the intestines can protect
against intestinal injury and influence social behavior, according
to new preclinical research. The findings extend a growing body of
work identifying a 'gut-immunity-brain axis,' a signaling system
that may have a wide range of effects on physiology in both health
and disease, influenced not only by the body's own cells but also
the resident microbes.



FULL STORY ==========================================================================
A specific group of fungi residing in the intestines can protect
against intestinal injury and influence social behavior, according to new preclinical research by scientists at Weill Cornell Medicine. The findings extend a growing body of work identifying a "gut-immunity-brain axis,"
a signaling system that may have a wide range of effects on physiology
in both health and disease, influenced not only by the body's own cells
but also the resident microbes.


==========================================================================
The study, published Feb. 16 in Cell, reveals a novel set of molecular
signals connecting fungi in the gut to their host's cells throughout
the body, including immune cells and neurons.

"We have made a direct link between a major immune pathway induced
by fungi in the lining of the intestine and signals in the nervous
system that impact animal behavior," said senior author Dr. Iliyan
Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute
for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

Drs. Dilek Colak, Melanie Johncilla and Megan Allen from Weill Cornell
Medicine and Dr. Rhonda K. Yantiss from Weill Cornell Medicine and NewYork-Presbyterian also contributed to this study.

The lining of the intestine must balance conflicting needs,
absorbing water and nutrients from food while acting as a barrier to
prevent the vast population of microbes in the gut from invading the bloodstream. Examining this system in a mouse model, the scientists
mapped the locations of different fungi within the intestine and found
that a unique consortium of fungi tends to accumulate at specific sites
near the gut epithelium, or lining, suggesting that these species have colonized the gut and interact closely with the nearby epithelial cells.

Mice carrying some of these fungi enjoyed better protection against events
that can disrupt the intestinal barrier, such as intestinal injury and bacterial infection. "There was fortification of those barrier functions
when we added that specific fungal community to mice," Dr. Iliev said.



========================================================================== Improving intestinal barrier integrity wasn't the only effect of the
fungi. In separate experiments, the team found that mice carrying the
fungal community in their gut displayed more social behavior than animals without these fungi.

Both effects appear to stem from the animals' own T cells, a type of
immune cell. The fungi cause T cells to secrete two immune signaling
proteins, cytokines IL-22 and IL-17. Fungi-induced IL-22 acts locally in
the epithelium, strengthening its barrier function, while IL-17 enters
the bloodstream and eventually reaches neurons, which have receptors
for it. Mice lacking the IL-17 receptor in their neurons don't exhibit
the social effects of fungal colonization.

"There is this harmony -- a kind of communication between or across
different types of organisms," Dr. Iliev said.

Now the investigators hope to explore that communication network
further. "We are trying to go deeper into the mechanisms of this
interaction, looking at the signals that are involved at the neuronal
level in different brain regions," said lead author Dr. Irina Leonardi,
an instructor of immunology in medicine in Dr. Iliev's laboratory at
the Jill Roberts Institute for Research in IBD.

One tantalizing possibility is that different microbial communities in
the gut could stimulate different regions of the brain and the immune
system, exerting distinct effects on their hosts' biology.

"This opens a whole new area to explore," Dr. Iliev said.

Irina Leonardi is supported though a CCF 568319 Research Fellowship
Award; Research in the Iliev laboratory is supported by US National
Institutes of Health grants (R01DK113136, R01DK121977, and R01AI163007),
the Leona M. and Harry B. Helmsley Charitable Trust, the Irma T. Hirschl
Career Scientist Award, the Crohn's and Colitis Foundation, and the
Burroughs Wellcome Fund PATH Award.Additional support for this study
was provided by Cure for IBD, the Glenn Greenberg and Linda Vester
Foundation, The Rosanne H. Silbermann Foundation, Pamela and Arthur
Sanders Family Foundation and the Jill Roberts Institute for Research
in IBD (https://robertsinstitute.weill.cornell.edu).

========================================================================== Story Source: Materials provided by Weill_Cornell_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Irina Leonardi, Iris H. Gao, Woan-Yu Lin, Megan Allen, Xin V. Li,
William
D. Fiers, Meghan Bialt De Celie, Gregory G. Putzel, Rhonda
K. Yantiss, Melanie Johncilla, Dilek Colak, Iliyan D. Iliev. Mucosal
fungi promote gut barrier function and social behavior via Type
17 immunity. Cell, 2022; DOI: 10.1016/j.cell.2022.01.017 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220216112216.htm

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