MaaT013 fecal microbiotherapy modulates key gastro-intestinal and immunological processes involved in GvHD pathogenesis in vitro and in vivo
Abstract
Background Acute graft-vs.-host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), where allogeneic donor T cells recognize recipient tissues as foreign and damage them. Gut microbiota disruption following allo-HCT has been associated with increased aGvHD incidence, severity, and mortality. Growing clinical evidence suggests the efficacy of fecal microbiotherapy to restore a healthy and diverse gut microbiota and to treat aGvHD. MaaT013 (Xervyteg ® ), a standardized allogeneic fecal microbiotherapy derived from pooled healthy human fecal microbiota, has demonstrated efficacy in mitigating steroid-refractory aGvHD in the Phase 2 HERACLES trial, and is currently being evaluated in the pivotal ARES trial in ruxolitinib-resistant aGvHD with gastrointestinal involvement. Methods Here, multi-omics analyses across complementary in vitro and in vivo models suggest that MaaT013 modulates biological processes involved in aGvHD pathogenesis. Results First, MaaT013-derived metabolites prevented inflammation-induced gut barrier alteration in an in vitro leaky gut model. Second, MaaT013 stimulated dendritic cell-mediated Tregs amplification and subsequent release of IL-10 and TGF-b in vitro . Third, beneficial bacteria from MaaT013 engrafted in the gut of germ-free mice, producing anti-inflammatory metabolites and restoring healthy gut physiology through immune rebalancing. Finally, MaaT013 delayed the appearance of aGvHD symptoms in a specific-pathogen free xenogeneic mouse model of aGvHD. Discussion Together, these results provide exploratory, multi-model evidence of MaaT013's potential to mitigate aGvHD by restoring microbial diversity, gut integrity, and immune homeostasis.
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BibTeX
@article{laperrousaz2026maat013,
title = {{MaaT013 fecal microbiotherapy modulates key gastro-intestinal and immunological processes involved in GvHD pathogenesis in vitro and in vivo}},
author = {Bastien Laperrousaz and Julie Reygner and Margaux de Seilhac and Antoine Sabourin and Cassandra Bompard and Cyrielle Gasc and Emmanuel Prestat and Benoît Levast and Charlotte Petitjean and Sophie Declomesnil and Emmanuelle Godefroy and Carole Schwintner and Nathalie Corvaïa and Robert Jenq and Ernst Holler},
journal = {Frontiers in Microbiology},
year = {2026},
month = sep,
doi = {10.3389/fmicb.2026.1920614},
url = {https://inserm.hal.science/inserm-05777958v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MaaT013 fecal microbiotherapy modulates key gastro-intestinal and immunological processes involved in GvHD pathogenesis in vitro and in vivo
AU - Bastien Laperrousaz
AU - Julie Reygner
AU - Margaux de Seilhac
AU - Antoine Sabourin
AU - Cassandra Bompard
AU - Cyrielle Gasc
AU - Emmanuel Prestat
AU - Benoît Levast
AU - Charlotte Petitjean
AU - Sophie Declomesnil
AU - Emmanuelle Godefroy
AU - Carole Schwintner
AU - Nathalie Corvaïa
AU - Robert Jenq
AU - Ernst Holler
PY - 2026
DA - 2026/09/14
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1920614
UR - https://inserm.hal.science/inserm-05777958v1
AB - Background Acute graft-vs.-host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), where allogeneic donor T cells recognize recipient tissues as foreign and damage them. Gut microbiota disruption following allo-HCT has been associated with increased aGvHD incidence, severity, and mortality. Growing clinical evidence suggests the efficacy of fecal microbiotherapy to restore a healthy and diverse gut microbiota and to treat aGvHD. MaaT013 (Xervyteg ® ), a standardized allogeneic fecal microbiotherapy derived from pooled healthy human fecal microbiota, has demonstrated efficacy in mitigating steroid-refractory aGvHD in the Phase 2 HERACLES trial, and is currently being evaluated in the pivotal ARES trial in ruxolitinib-resistant aGvHD with gastrointestinal involvement. Methods Here, multi-omics analyses across complementary in vitro and in vivo models suggest that MaaT013 modulates biological processes involved in aGvHD pathogenesis. Results First, MaaT013-derived metabolites prevented inflammation-induced gut barrier alteration in an in vitro leaky gut model. Second, MaaT013 stimulated dendritic cell-mediated Tregs amplification and subsequent release of IL-10 and TGF-b in vitro . Third, beneficial bacteria from MaaT013 engrafted in the gut of germ-free mice, producing anti-inflammatory metabolites and restoring healthy gut physiology through immune rebalancing. Finally, MaaT013 delayed the appearance of aGvHD symptoms in a specific-pathogen free xenogeneic mouse model of aGvHD. Discussion Together, these results provide exploratory, multi-model evidence of MaaT013's potential to mitigate aGvHD by restoring microbial diversity, gut integrity, and immune homeostasis.
SN - 1664-302X
SN - 1664-302X
ER -