Methods and compositions for microbial engraftment
Inventors
Eid, John S. • Cutcliffe, Colleen • Bullard, James H. • JUSTICE, Nicholas • GINES, Jessica • TYAGI, Surabhi • SCHICKLBERGER, Marcus F. • CHENG, Andrew T. • MCMURDIE, Paul • Sieber, Christian
Assignees
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Publication Number
US-12343360-B2
Publication Date
2025-07-01
Expiration Date
Abstract
The disclosure provides compositions and methods for therapeutic administration of the compositions to treat comorbidities associated with gut dysbiosis. The disclosure also provides compositions and methods for increasing engraftment of administered microbes. The disclosure also provides methods for stool sample collection.
Core Innovation
The invention relates to increasing engraftment of Eubacterium hallii in the gut of a mammalian subject by administering Eubacterium hallii together with Akkermansia muciniphila. The core concept is that a mucin-degrading microbe supports or enables engraftment of a butyrate-producing microbe in the gut, and the described approach includes assessing whether engraftment of Eubacterium hallii is increased in the subject’s gut.
The problem addressed is gut dysbiosis and microbial engraftment that is insufficient, particularly for butyrate-producing microbes. The description emphasizes that engraftment of the butyrate-producing microbe is linked to the presence of the mucin-degrading microbe, and that engraftment is evaluated using microbiome profiling and nucleic-acid detection.
The described embodiments include formulations for administering the microbes to the gut, including oral enteric capsules and substantially dry microbes, and optional inclusion of a prebiotic such as inulin. The document also describes monitoring engraftment in stool and using nucleic-acid detection, including qPCR and sequencing with strain-specific primers, to detect and quantify the microbes.
Claims Coverage
The independent claim family member is directed to a method that includes administering Eubacterium hallii with Akkermansia muciniphila and measuring increased engraftment of Eubacterium hallii in a mammalian subject. The claim set includes 7 inventive features, with dependent refinements covering quantitative and temporal measurement criteria, a presence condition tied to Akkermansia muciniphila, and optional oral delivery formulation and inulin adjunct.
Co-administration of Eubacterium hallii with Akkermansia muciniphila to increase engraftment
Administering to the gut of the mammalian subject Eubacterium hallii and Akkermansia muciniphila.
Measuring increased engraftment of Eubacterium hallii in the gut
Measuring increased engraftment of Eubacterium hallii in the gut of the subject.
Quantitative engraftment increase threshold
Increasing engraftment characterized by at least about 5%.
Engraftment measured as increased relative abundance for a defined post-cessation window
Measuring increased engraftment as an increased relative abundance of the butyrate producing microbe Eubacterium hallii for more than 4 weeks after administration has ceased.
Engraftment occurs only in the presence of Akkermansia muciniphila
Eubacterium hallii only engrafts in a presence of Akkermansia muciniphila.
Oral delivery formulation of the microbes
Eubacterium hallii and Akkermansia muciniphila are formulated for oral delivery.
Optional inulin prebiotic adjunct
The prebiotic used is inulin.
The claim coverage centers on co-administering Eubacterium hallii with Akkermansia muciniphila to increase gut engraftment, followed by measuring increased engraftment of Eubacterium hallii. Additional refinements specify a quantitative threshold, a relative-abundance measurement basis over a post-administration time window, an engraftment condition requiring Akkermansia muciniphila presence, and optional oral delivery formulations and an optional inulin prebiotic adjunct.
Stated Advantages
Increasing engraftment of Eubacterium hallii in the gut of a mammalian subject.
Measuring and detecting increased engraftment of Eubacterium hallii in the gut of the subject after administration.
Ensuring Eubacterium hallii engrafts only in the presence of Akkermansia muciniphila.
Documented Applications
Improving microbial engraftment of butyrate-producing microbes, including Eubacterium hallii, in the gut as part of addressing gut dysbiosis and butyrate-associated disorders.
Human open-label escalation trial described as indicating enhanced engraftment during and after washout, with stool-based monitoring using nucle-acid detection and strain-specific primers.
Rodent study described showing that butyrate producer engraftment requires the mucin-degrading microbe, supported by strain-specific nucleic-acid probes and washout or timepoint analysis.
Administration and measurement of Eubacterium hallii engraftment in the gut of a mammalian subject, including a preclinical rodent study with oral dosing and measurement of GI engraftment.
Human clinical study methods and monitoring are described in the document [procedural detail omitted for safety].
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