COMPOSITIONS AND METHODS FOR REDUCING CYTOKINE EXPRESSION
Provided herein are methods and compositions related to Prevotella bacteria for the reduction of IL-8, IL-6, IL-Iβ, and/C or TNFα expression and/or for the treatment of viral infections.
1 . A method of reducing IL-8, IL-6, IL-1β, and/or TNFα expression levels in a human subject in need thereof, comprising orally administering to the subject a Prevotella histicola strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
2 . A method of treating a viral infection in a subject comprising orally administering to the subject a Prevotella histicola strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
3 . A method of treating COVID-19 in a subject comprising orally administering to the subject a Prevotella histicola strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
4 . The method of any one of claims 1 to 3 , wherein the Prevotella histicola strain is the Prevotella Strain B (NRRL accession number B 50329).
5 . The method of any one of claims 1 to 4 , wherein the subject is administered at least 8×10 10 total cells of the Prevotella histicola strain.
6 . The method of any one of claims 1 to 4 , wherein the subject is administered at least 1.6×10 11 total cells of the Prevotella histicola strain.
7 . The method of any one of claims 1 to 4 , wherein the subject is administered at least 8×10 11 total cells of the Prevotella histicola strain.
8 . The method of any one of claims 1 to 4 , wherein the subject is administered between 8×10 10 and 8×10 11 total cells per day of the Prevotella histicola strain.
9 . The method of any one of claims 1 to 4 , wherein the subject is administered between 1.6×10 11 and 8×10 11 total cells per day of the Prevotella histicola strain.
10 . The method of any one of claims 1 to 4 , wherein the subject is administered about 8×10 10 total cells per day of the Prevotella histicola strain.
11 . The method of any one of claims 1 to 4 , wherein the subject is administered about 1.6×10 11 total cells per day of the Prevotella histicola strain.
12 . The method of any one of claims 1 to 4 , wherein the subject is administered about 8×10 11 total cells per day of the Prevotella histicola strain.
13 . The method of any one of claims 1 to 12 , wherein the Prevotella histicola strain is administered in the form of one or more enteric-coated capsules.
14 . The method of claim 13 , wherein the capsule comprises a pH-sensitive enteric coating that such that the contents of the capsule are released into the human subject's duodenum and jejunum.
15 . The method of any one of claims 1 to 12 , wherein the Prevotella histicola strain is administered in the form of one or more enteric coated tablets.
16 . The method of any one of claims 1 to 12 , wherein the Prevotella histicola strain is administered in the form of one or more enteric-coated mini-tablets.
17 . The method of claim 16 , wherein the one or more enteric-coated mini-tablets are administered in one or more a non-enteric-coated capsules.
18 . The method of any one of claims 1 to 17 , wherein the subject is orally administered a plurality of doses of the Prevotella histicola strain.
19 . The method of claim 18 , wherein the human subject is administered daily doses of the Prevotella histicola strain for at least 7 days.
20 . The method of claim 18 , wherein the human subject is administered daily doses of the Prevotella histicola strain for at least 14 days.
21 . The method of claim 18 , wherein the human subject is administered daily doses of the Prevotella histicola strain for at least 28 days.
22 . The method of claim 18 , wherein the human subject is administered twice-daily doses of the Prevotella histicola strain.
23 . The method of claim 22 , wherein the human subject is administered twice-daily doses of the Prevotella histicola strain for at least 7 days.
24 . The method of claim 22 , wherein the human subject is administered twice-daily doses of the Prevotella histicola strain for at least 14 days.
25 . The method of claim 22 , wherein the human subject is administered twice-daily doses of the Prevotella histicola strain for at least 28 days.
26 . The method of any one of claims 1 to 25 , wherein the subject has been infected with a coronavirus, an influenza virus, and/or a respiratory syncytial virus.
27 . The method of any one of claims 1 to 26 , wherein the subject has been infected with SARS-CoV-2.
28 . The method of claim 27 , wherein the subject has COVID-19.
29 . The method of any one of claims 1 to 28 , wherein the subject is traveling to a region where SARS-CoV-2 infection is endemic.
30 . The method of any one of claims 1 to 29 , wherein the subject has been exposed to a source infected with a coronavirus, an influenza virus, and/or a respiratory syncytial virus.
31 . The method of any one of claims 1 to 30 , wherein the subject has been exposed to a source infected with SARS-CoV-2.
32 . The method of claim any one of claims 1 to 31 , further comprising administering to the subject an antiviral medication.
33 . The method of claim 32 , wherein the antiviral medication is ribavirin, neuraminidase inhibitor, protease inhibitor, recombinant interferons, antibodies, oseltamivir, zanamivir, peramivir or baloxavir marboxil.
34 . The method of any one of claims 1 to 33 , further comprising administering to the subject an anti-inflammatory agent.
35 . The method of claim 34 , wherein the anti-inflammatory agent is an NSAID or an anti-inflammatory steroid.
36 . The method of claim any one of claims 1 to 35 , further comprising administering to the subject hydroxychloroquine, chloroquine, remdesivir, tocilizumab and/or sarilumab.
37 . A method of identifying a subject as being at risk for increased severity of a disease or condition, the method comprising determining expression levels IL-8, IL-6, IL-1β, and/or TNFα in a sample from the subject, wherein elevated expression levels of IL-8, IL-6, IL-1β, and/or TNFα in the sample indicate that the subject is at of increased severity of the disease or condition.
38 . The method of claim 37 , wherein the disease or condition is a coronavirus infection, an influenza virus infection, and/or a respiratory syncytial virus infection.
39 . The method of claim 37 , wherein the disease or condition is SARS-CoV-2 infection.
40 . The method of any one of claims 37 to 39 , further comprising treating the subject for the disease or condition.
41 . The method of claim 40 , wherein the treatment comprises orally administering to the subject a Prevotella histicola strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
42 . The method of claim 41 , wherein the Prevotella histicola strain is the Prevotella Strain B (NRRL accession number B 50329).
43 . The method of any one of claims 40 to 42 , wherein the treatment comprises administering the subject an antiviral medication.
44 . The method of claim 43 , wherein the antiviral medication is ribavirin, neuraminidase inhibitor, protease inhibitor, recombinant interferons, antibodies, oseltamivir, zanamivir, peramivir or baloxavir marboxil.
45 . The method of any one of claims 40 to 44 , wherein the treatment comprises administering the subject an anti-inflammatory agent.
46 . The method of claim 45 , wherein the anti-inflammatory agent is an NSAID or an anti-inflammatory steroid.