A microbiome-based food allergy therapy?

La Jolla, CA and BOSTON—Consortia TX announced today the publication of comprehensive research into the potential for microbial therapies to prevent and treat disease and food allergies, in the peer-reviewed medical journal Nature Medicine. The research describes major advances in the science behind Consortia TX’s effort to develop a therapy to treat and prevent food allergies.

The article links changes in the microbiome to food allergies in children and overviews the development of consortia of therapeutic microbes that completely suppressed this disorder in a preclinical animal model, with detailed analysis of the related host mechanisms underlining the therapeutic effect. The article, entitled “Microbiota Therapy Acts Via a Regulatory T Cell MyD88/RORγt Pathway to Suppress Food Allergy,” details extensive research carried out by Talal Chatila M.D., MSc.; Lynn Bry, M.D.. Ph.D.; Rima Rachid M.D.; and Georg Gerber, M.D., Ph.D.

These researchers are the scientific team behind the company. Consortia TX is now building on the article findings to develop its proprietary microbial therapeutic, CTX-944, a live biotherapeutic product for the reversal of food allergy.

“We are thrilled to publish breakthrough research and data focused on the causal links between the microbiome and food allergy, which demonstrated that a live biotherapeutic product has the potential to suppress responses to allergens at the cellular level,” said lead author Chatila, co-founder of Consortia TX.

Along with first co-authors Azza Abdel-Gadir, Ph.D., Emmanuel Stephen-Victor, Ph.D., and their colleagues at the Boston Children’s Hospital, Chatila undertook the genetic, immunological and microbial therapeutic studies on germ-free and allergy-prone mice, and on immune cells of food allergic human subjects. Based on this extensive research, the scientific founders of Consortia TX believe that our microbiome has the ability to fundamentally change cell types to suppress reactions, ultimately training the immune system away from an inflammatory state.

In a clinical study at Boston Children’s Hospital led by Dr. Rima Rachid, co-senior author on the paper and advisor to Consortia TX, the team carried out serial sampling of the gut bacteria of infants and young children with food allergies and compared results to those of healthy control subjects.

“Our studies confirmed the presence of changes in the gut bacteria of food allergic subjects which, when tested in mouse models, were found critical for the development of disease,” mentioned Rachid. “The research thus established a link between the disruption of a healthy gut microbiome and the development of food allergy.”

“We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated. Therapy with Clostridiales species impacted by dysbiosis, either as a consortium or as monotherapy with Subdoligranulum variabile, suppressed FA in mice as did a separate immunomodulatory Bacteroidales consortium,” points out the article abstract. “Bacteriotherapy induced expression by regulatory T (Treg) cells of the transcription factor ROR-γt in a MyD88-dependent manner, which was deficient in FA infants and mice and ineffectively induced by their microbiota. Deletion of Myd88 or Rorc in Treg cells abrogated protection by bacteriotherapy. Thus, commensals activate a MyD88/ROR-γt pathway in nascent Treg cells to protect against FA, while dysbiosis impairs this regulatory response to promote disease.”

In parallel, co-senior author Bry led a team at Brigham and Women’s Hospital that completed the microbiologic portions of the study, noting that “We identified culturable human-origin bacteria that modulate the immune system to become tolerant to food allergens.”

Co-first author and company co-founder Gerber, in his lab at Brigham and Women’s Hospital, designed computational algorithms to define the temporal dynamics of the microbiota and its relationship to food allergy. Back in January, Gerber was awarded a 5-year, $1.5 million National Institutes of Health grant to advance machine learning and software tools for longitudinal microbiome studies.

“By examining microbiomes at many time-points rather than just one snapshot, our team was able to narrow down the commensal bacteria that may prevent food allergy from hundreds to a short list that we then developed into therapeutic consortia,” Gerber added.

ConsortiaTX plans to incorporate the resulting open-source tools to help ConsortiaTX refine their CTX-944 therapy, and enhance interpretation of clinical results coming from ConsortiaTX’s upcoming Phase 1b trial.

“The ultimate goal for ConsortiaTX is to develop therapeutics to reverse food allergies,” added Bry in a press release. “The algorithmic approaches being developed will enhance the ability of ConsortiaTX and others to advance live biotherapeutic products to the clinic. Dr. Gerber’s expertise is a tremendous asset to the company as it integrates his tools for the development of CTX-944.”