Vanderbilt University

New York University

Enteric Research Laboratories Inc.

Other

University of Connecticut

Oravax, Inc.

Martin J Blaser

Timothy L Cover

Stuart A Thompson

Murali K Tummuru

Laura M Cox

Ilseung Cho

Harry Kleanthous

Geraldine G Miller

Richard M Peek, Jr

Thomas Wood

Zhi H Pei

Marcus B Jones

Dacheng Ren

Zhan Gao

Richard T Ellison, Iii

Mikio Karita

Guillermo I Perez-Perez

Smita A Sharma

Zhiheng Pei

Joel Dworkin

The application relates to methods based on modulating mammalian intestinal microbiota and related probiotic and prebiotic compositions. Specifically, the application relates to the use of novel bacterial generaand, including their species() and(), respectively, and closely related OTUs within the family Erysipelotrichaceae that resemble eitherspp. orspp. with 90% 16S rRNA sequence identity, for modulating weight and intestinal inflammation and immunity (including modulating intestinal immune gene expression such as, e.g., modulating expression of ROR&#x3b3;T, IL-17A, IL-17F, RegIII&#x3b3;, Relm&#x3b2;, and Def&#x3b2;), as well as for treatment and diagnosis of (i) obesity and related conditions such as metabolic syndrome and diabetes mellitus; (ii) allergic and autoimmune diseases, and (iii) gastrointestinal disorders (such as, e.g., inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, and celiac disease).

Probiotic compositions for improving metabolism and immunity

The present invention relates to characterizing changes in mammalian bacterial gastrointestinal, cutaneous and nasal microbiota associated with antibiotic treatment and various disease conditions (such as asthma, allergy, obesity, metabolic syndrome, gastrointestinal reflux disease (GERD), eosinophilic esophagitis, gastro-esophageal junction adenocarcinomas (GEJAC), infections due to bacteria that are resistant to antibiotics, including Methicillin-resistant(MRSA),vancomycin-resistant enterococci, etc.) and related diagnostic and therapeutic methods. Therapeutic methods of the invention involve the use of live bacterial inoculants that are capable of restoring healthy mammalian bacterial gastrointestinal, skin, and nasal microbiota.

Compositions and methods for restoring gastrointestinal microbiota following antibiotic treatment

The present invention relates to characterizing changes in mammalian intestinal microbiota associated with associated with high-fat and low-fat diets and with diets containing hydroxypropylmethylcellulose (HPMC) and related methods for diagnosing, preventing and treating obesity and related conditions such as metabolic syndrome and diabetes mellitus. Therapeutic methods of the invention involve the use of probiotics, and/or prebiotics, and/or narrow spectrum antibiotics/anti-bacterial agents that are capable of restoring healthy mammalian bacterial intestinal microbiota.

Compositions and methods for treating obesity and related disorders by characterizing and restoring mammalian bacterial microbiota

The present invention relates to characterizing changes in mammalian gastrointestinal microbiota associated with antibiotic treatment and various disease conditions (such as obesity, metabolic syndrome, insulin-deficiency or insulin-resistance related disorders, glucose intolerance, diabetes, non-alcoholic fatty liver, abnormal lipid metabolism, short stature, osteoporosis, and other disorders of bone formation and mineralization, etc.) and related diagnostic and therapeutic methods. Therapeutic methods of the invention involve the use of probiotics, prebiotics, or narrow spectrum antibiotics/anti-bacterial agents that are capable of restoring healthy mammalian bacterial gastrointestinal microbiota.

Methods for treating bone disorders by characterizing and restoring mammalian bacterial microbiota

The present invention relates to methods for characterization of bacterial skin microbiota to provide diagnostic, therapeutic, and preventive measures for alleviating skin conditions. In certain embodiments, the invention relates to characterization of bacterial skin microbiota associated with psoriasis and related diagnostic, therapeutic, and preventive measures for alleviating psoriasis. These methods will be useful for detecting, diagnosing, and monitoring individuals who have or are at risk of certain skin conditions.

Diagnostic and treatment methods for characterizing bacterial microbiota in skin conditions

The present invention pertains to the discovery thatpossesses a luxS gene that encodes a functional LuxS polypeptide, and thatsynthesizes a functional AI-2 quorum-sensing molecule. The invention provides mutantbacteria lacking the function of the luxS gene, which do not produce a functional AI-2 molecule and have growth defects compared to wild-type. The invention also concerns methods for inhibiting the growth of, or for preventing or treatinginfection, by inhibiting the activity of theLuxS polypeptide, or by exposure of theto furanone. In particular, the invention concerns the use of furanone, a compound that inhibits AI-2-mediated quorum-sensing, to inhibit the growth of, to inhibittoxin production, particularly that of protective antigen, and to prevent or treatinfection. The invention also provides methods to preventinfection, or enhance an immune response toinfection, by administering a vaccine comprising acell in which the luxS gene is mutated.

[object Object]

The present invention provides a mutant strain in which one or more sapA homologs are altered by an inserted DNA cassette so that the encoded S-layer proteins represent a chimera between the native S-layer proteins and a heterologous peptide encoded by the inserted cassette. Preferably, the heterologous peptide is an immunogen of a pathogen and the mutant strain can be used to immunize a host to develop mucosal and systemic immune responses to such immunogen.

Method of delivering antigens for vaccination with a live vector

The invention provides the dapE gene of and dapE mutants and to methods of using the mutants to express foreign genes and immunize against foreign agents. The dapE gene can consist of the nucleotide sequence defined in SEQ ID NO:3. Nucleic acids of the gidA gene and ORF 2 of are provided. Examples of these nucleic acids can be found in SEQ ID NO:1 and SEQ ID NO:5, respectively. Having provided these nucleic acids, hybridizing nucleic acids in accord with the description of hybridizing nucleic acids of dapE are also provided.

dapE gene on Helicobacter pylori and dapE&minus; mutant strains of Helicobacter pylori

The present invention provides an isolated nucleic acid encoding an approximately 120-128 kilodalton antigen of Helicobacter pylori, or an antigenic fragment thereof, wherein the antigen is associated with peptic ulceration. The present invention also provides methods of detecting the presence of a Helicobacter pylori strain possessing the 120-128 kilodalton antigen in a subject, comprising the steps of contacting an antibody-containing sample from the subject with a detectable amount of the tagA antigen or antigenic polypeptide of the present invention and detecting the binding of the antigen or fragment and the antibody. The detection of a strain expressing the TagA antigen is an indication of predisposition to peptic ulceration and gastric carcinoma. A mutant H. pylori not expressing a functional TagA antigen is also provided.

TagA gene and methods for detecting predisposition to peptic ulceration

A purified IceA protein of Helicobacter pylori is provided. The protein is expressed as either an IceA 1 or an IceA 2 variant. A purified polypeptide fragment of the IceA protein is also provided. An antigenic fragment of IceA is provided. An isolated nucleic acid that encodes an IceA protein of H. pylori is provided. A nucleic acid that encodes an IceA 1 variant and a nucleic acid that encodes an IceA 2 variant is also provided. Fragments of the iceA gene are provided. A method of detecting the presence of an antibody against H. pylori in a sample is provided. The method comprises the following steps: a) contacting the sample with a purified IceA protein of H. pylori or a H. pylori-specific fragment thereof; and b) detecting the binding of the antibody in the sample to the protein or fragment, the detection of binding indicating the presence in the sample of antibodies against H. pylori. A method of detecting the presence of an antibody against an ulcerative Helicobacter pylori strain in a sample is also provided.

iceA gene and related methods

This invention relates to a purified Helicobacter pylori vacuolating toxin and methods to use this toxin to produce protective antibodies against H. pylori infection. Antiserum to this antigen can be used to detect the toxin. Methods to detect anti-toxin antibodies determine the susceptibility of a patient to develop peptic ulcer disease, gastric carcinoma, or other clinical consequences of H. pylori infection.

Growing community of inventors

Nashville, TN, United States of America

Martin J Blaser