Granted Patent
B2
US 12,257,235 · App. 18/537,398 · Granted Mar 25, 2025
Methods and materials for using ruminococcus gnavus or clostridium sporogenes to treat gastrointestinal disorders
Inventors:
Purna C. Kashyap (Rochester, MN); Michael Fischbach (Portola Valley, CA); Brianna B. Williams (Oakland, CA)
Assignees:
Mayo Foundation for Medical Education and Research; The Regents of the University of California
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Abstract
This document provides materials and methods related to bacterial compositions containing at least one bacterial organism having tryptophan decarboxylase activity. For example, bacterial compositions containing at least one bacterial organism having tryptophan decarboxylase activity and methods for using such bacterial compositions to improve gastrointestinal epithelial function and/or to treat gastrointestinal disorders are provided.
Claims (13)
1. A method for treating a gastrointestinal disorder in a human, wherein said method comprises:
(a) identifying said human as having said gastrointestinal disorder, and
(b) administering a composition comprising tryptophan and at least one live Ruminococcus gnavus to said human under conditions wherein gastrointestinal function of said human is improved.
2. The method of claim 1 , wherein said gastrointestinal disorder is irritable bowel syndrome.
3. The method of claim 1 , wherein said composition comprises at least one bacterial organism comprising exogenous tryptophan decarboxylase activity.
4. The method of claim 3 , wherein said at least one bacterial organism comprising exogenous tryptophan decarboxylase activity is Escherichia coli or Bacteroides thetaiotaomicron.
5. The method of claim 1 , wherein said composition is a pill, tablet, or capsule.
6. The method of claim 5 , wherein said pill, tablet, or capsule is configured to deliver said live Ruminococcus gnavus to the intestines of said human.
7. The method of claim 3 , wherein said at least one bacterial organism comprises exogenous nucleic acid encoding a polypeptide having tryptophan decarboxylase activity.
8. The method of claim 7 , wherein said exogenous nucleic acid encodes a tryptophan decarboxylase derived from Ruminococcus gnavus.
9. The method of claim 1 , wherein from about 95 to about 100 percent of bacteria of said composition comprise tryptophan decarboxylase activity.
10. The method of claim 1 , wherein said composition comprises Prevotella coprii, Bifidobacterium infantis, Lactobacillus rhamnosis GG, Lactobacillus plantarum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus bulgaricus, Streptococcus thermophilus , or Faecalibacterium prauznitzii.
11. The method of claim 1 , wherein said at least one live Ruminococcus gnavus is R. gnavus ATCC 29149.
Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 6, 2024
From: KASHYAP, PURNA C.; FISCHBACH, MICHAEL
To: MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
Reel/Frame 069504/0986 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 6, 2024
From: MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
To: FISCHBACH, MICHAEL
Reel/Frame 069504/0993 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 6, 2024
From: FISCHBACH, MICHAEL
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 069505/0019 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 6, 2024
From: WILLIAMS, BRIANNA B.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 069505/0021 →
CONFIRMATORY LICENSE
Recorded Jan 11, 2024
From: MAYO CLINIC ROCHESTER
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066272/0085 →
Continuity (5)
Provisional Application
62204270
· Aug 12, 2015
References Cited (59)
US 5766879A
· Gerald et al.
· 1998
[cited by applicant]
US 6331401B1
· Gerald et al.
· 2001
[cited by applicant]
US 20080241226A1
· Abeln et al.
· 2008
[cited by applicant]
US 20090325949A1
· Barlow et al.
· 2009
[cited by applicant]
US 20160000837A1
· Rey et al.
· 2016
[cited by applicant]
WO WO2006029389
· 2006
[cited by applicant]
WO WO2012142605A1
· 2012
[cited by examiner]
Bell, “Treatment with gentamicin monitored by serum antibiotic assay,” Med J Aust., 2(13):481-484, Sep. 25, 1976.
[cited by applicant]
Bhattacharjee and Snell, “Pyridoxal 5'-phosphate-dependent histidine decarboxylase. Mechanism of inactivation by alpha-fluoromethylhistidine,” J Biol Chem., 265(12):6664-6668, Apr. 25, 1990.
[cited by applicant]
Bianchetti et al., “Effects of tyramine on blood pressure and plasma catecholamines in normal and hypertensive subjects,” Klin Wochenschr., 60(9):465-470, May 3, 1982.
[cited by applicant]
Burkhard et al., “Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase,” Nat Struct Biol., 8(11):963-967, Nov. 2001.
[cited by applicant]
Fenalti et al., “GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop,” Nat Struct Mol Biol., 14(4):280-286, Epub Mar. 25, 2007.
[cited by applicant]
Gaddum, “Tryptamine receptors,” J Physiol., 119(2-3):363-368, Feb. 27, 1953.
[cited by applicant]
Gallagher et al., “Refined structure of the pyruvoyl-dependent histidine decarboxylase from Lactobacillus 30a,” J Mol Biol., 230(2):516-528, Mar. 20, 1993.
[cited by applicant]
GenPept Accession: EDU35915, “pyridoxal-dependent decarboxylase domain protein [Clostridium sporogenes ATCC 15579],” Aug. 15, 2012, 3 pages.
[cited by applicant]
GenPept Accession: EGG84852, “hypothetical protein HMPREF9477_00579 [Lachnospiraceae bacterium 2_1_46FAA],” Jun. 10, 2013 HMPREF9477_00579, Jun. 28, 2011, 2 pages.
[cited by applicant]
GenPept Accession: WP_004612385, “Multispecies: glutamate decarboxylase [Clostridiales],” Jun. 9, 2014, 1 page.
[cited by applicant]
GenPept Accession: WP_007718072, “glutamate decarboxylase [[Clostridium] asparagiforme],” May 26, 2013, 1 page.
[cited by applicant]
GenPept Accession: YP_006429963, “PLP-dependent enzyme, glutamate decarboxylase [Desulfitobacterium dehalogenans ATCC 51507],” Dec. 17, 2014, 2 pages.
[cited by applicant]
GenPept Accession: ZP_02040762 (GI No. 154503702), “hypothetical protein RUMGNA 01526 [Ruminococcus gnavus ATCC 29149]” Nov. 9, 2010, 1 page.
[cited by applicant]
GenPept Accession: ZP_05855305, “putative aromatic-L-amino-acid decarboxylase [Blautia hansenii DSM 20583],” Nov. 27, 2012, 2 pages.
[cited by applicant]
Gershon and Tack, “The serotonin signaling system: from basic understanding to drug development for functional GI disorders,” Gastroenterology, 132(1):397-414, Jan. 2007.
[cited by applicant]
Giardina et al., “Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases,” Proc Natl Acad Sci U S A., 108(51):20514-20519, Epub Dec. 5, 2011.
[cited by applicant]
Goldszmid et al., “The price of immunity,” Nat Immunol., 13(10):932-938, Epub Sep. 18, 2012.
[cited by applicant]
Hayashi et al., “Pyridoxal 5'-phosphate-dependent histidine decarboxylase. Inactivation by alpha-fluoromethylhistidine and comparative sequences at the inhibitor-and coenzyme-binding sites,” J Biol Chem., 261(24):11003-…
[cited by applicant]
Hoffman et al., “Activation of colonic mucosal 5-HT(4) receptors accelerates propulsive motility and inhibits visceral hypersensitivity,” Gastroenterology, 142(4):844-854.e4, Epub Jan. 4, 2012.
[cited by applicant]
Husebye et al., “Intestinal microflora stimulates myoelectric activity of rat small intestine by promoting cyclic initiation and aboral propagation of migrating myoelectric complex,” Dig Dis Sci., 39(5):946-956, May 199…
[cited by applicant]
Ishihara et al., “Probing the role of tryptophan-derived secondary metabolism in defense responses against Bipolaris oryzae infection in rice leaves by a suicide substrate of tryptophan decarboxylase,” Phytochemistry, 7…
[cited by applicant]
John et al., “Pyridoxal phosphate-dependent enzymes,” Biochim Biophys Acta., 1248(2):81-96, Apr. 27, 1995.
[cited by applicant]
Kashyap et al., “Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice,” Gastroenterology, 144(5):967-977, Epub Feb. 1, 2013.
[cited by applicant]
Katoh et al., “MAFFT: iterative refinement and additional methods,” Methods Mol Biol., 1079:131-146, 2014.
[cited by applicant]
Kim, “5-Hydroxytryptamine4 receptor agonists and colonic motility,” J Smooth Muscle Res., 45(1):25-29, Feb. 2009.
[cited by applicant]
Komori et al., “Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase,” J Biol Chem., 287(34):29175-29183, Epub Jul. 5, 2012.
[cited by applicant]
Manabe et al., “New-generation 5-HT4 receptor agonists: potential for treatment of gastrointestinal motility disorders,” Expert Opin Investig Drugs, 19(6):765-775, Jun. 2010.
[cited by applicant]
Mawe et al., “Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets,” Nat Rev Gastroenterol Hepatol., 10(8):473-486, Epub Jun. 25, 2013.
[cited by applicant]
Metzner, “Serotonin, L-tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1,” Faseb J., 19(11):1468-1473, Sep. 2005.
[cited by applicant]
O'Hara et al., “The gut flora as a forgotten organ,” EMBO Rep., 7(7):688-693, Jul. 2006.
[cited by applicant]
Pettersen et al., “UCSF Chimera—a visualization system for exploratory research and analysis,” J Comput Chem., 25(13):1605-1612, Oct. 2004.
[cited by applicant]
Reigstad and Kashyap, “Beyond phylotyping: understanding the impact of gut microbiota on host biology,” Neurogastroenterol Motil., 25(5):358-372, May 2013.
[cited by applicant]
Reigstad et al., “Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells,” FASEB J., 29(4):1395-1403, Epub Dec. 30, 2014, Print Apr. 2015.
[cited by applicant]
Roager et al. “ Microbial tryptophan catabolites in health and disease” Nature Communications I (2018)9:32941 DOI: 10.1038/s41467-018-05470-4 I www.nature.com/naturecommunications. (Year: 2018).
[cited by applicant]
Samuel et al., “Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41,” Proc Natl Acad Sci U S A., 105(43):16767-16772, Epub Oct. 17, 2008.
[cited by applicant]
Schirmer et al., “Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides,” Proc Natl Acad Sci U S A., 103(11):4234-9. Epub Mar. 6, 2006.
[cited by applicant]
Schneider et al., “The manifold of vitamin B6 dependent enzymes,” Structure, 8(1):R1-R6, Jan. 15, 2000.
[cited by applicant]
Shanahan, “The host-microbe interface within the gut,” Best Pract Res Clin Gastroenterol., 16(6):915-931, Dec. 2002.
[cited by applicant]
Sharma et al., “The diet and gut microflora influence the distribution of enteroendocrine cells in the rat intestine, ” Experientia, 52(7):664-670, Jul. 15, 1996.
[cited by applicant]
Takaki et al., “Physiological responses of guinea-pig myenteric neurons secondary to the release of endogenous serotonin by tryptamine,” Neuroscience, 16(1):223-240, Sep. 1985.
[cited by applicant]
UniProtKB: CLOSPO_02083, Oct. 31, 2012, 1 page.
[cited by applicant]
Uribe et al., “Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat,” Gastroenterology, 107(5):1259-1269, Nov. 1994.
[cited by applicant]
van Poelje et al., “Pyruvoyl-dependent enzymes,” Annu Rev Biochem., 59:29-59, 1990.
[cited by applicant]
Weissbach et al., “Formation of indole-3-acetic acid and tryptamine in animals: a method for estimation of indole-3-acetic acid in tissues,” J Biol Chem., 234(1):81-86, Jan. 1959.
[cited by applicant]
Wikoff et al., “Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites,” Proc Natl Acad Sci U S A., 106(10):3698-3703, Epub Feb. 20, 2009.
[cited by applicant]
Williams et al., “Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine,” Cell Host Microbe., 16(4):495-503, Epub Sep. 25, 2014.
[cited by applicant]