METHODS OF DECREASING DYSBIOSIS AND RESTORING A MICROBIOME
Provided herein are methods for decreasing dysbiosis, restoring the microbiome, and/or increasing recovery of a healthy microbiome (e.g. following a dysbiosis inducing event), by administering pharmaceutical compositions to a subject. Also provided are methods for protecting the microbiome of a subject and/or colonizing the microbiome of a subject by administering pharmaceutical compositions to the subject.
1 .- 217 . (canceled)
218 . A method for treating or preventing Clostridium difficile infection in a subject, the method comprising:
administering vancomycin to the subject, followed by administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a purified bacterial mixture, wherein the purified bacterial mixture comprises:
(i) a bacterial strain belonging to Clostridium bolteae;
(ii) a bacterial strain belonging to Anaerotruncus colihominis;
(iii) a bacterial strain belonging to Drancourtella massiliensis or Sellimonas intestinalis;
(iv) a bacterial strain belonging to Clostridium symbiosum;
(v) a bacterial strain belonging to Blautia producta;
(vi) a bacterial strain belonging to Dorea longicatena;
(vii) a bacterial strain belonging to Clostridium innocuum ; and
(viii) a bacterial strain belonging to Flavonifractor plautii,
wherein the vancomycin is administered in multiple doses prior to administering the pharmaceutical composition,
wherein the pharmaceutical composition is administered in multiple doses on consecutive days, and
wherein a total of at least 4.0×10 10 colony forming units (CFUs) or at least 1.1×10 11 CFUs of bacteria are administered to the subject.
219 . The method of claim 218 , wherein a total of at least 4.0×10 10 CFUs of bacteria are administered as at least five doses over at least five days.
220 . The method of claim 218 , wherein a total of at least 1.1×10 11 CFUs of bacteria are administered as at least fourteen doses over at least fourteen days.
221 . The method of claim 218 , wherein each of the multiple doses of the pharmaceutical composition comprises at least 8.0×10 9 CFUs.
222 . The method of claim 221 , wherein each of the multiple doses of the pharmaceutical composition comprises the administration of 10 capsules, wherein each capsule comprises at least 8.0×10 8 CFUs.
223 . The method of claim 218 , wherein the C. difficile infection is a primary C. difficile infection.
224 . The method of claim 218 , wherein the C. difficile infection is a recurrence of C. difficile infection.
225 . The method of claim 218 , wherein the method is a method of preventing recurrence of C. difficile infection.
226 . The method of claim 218 , wherein the vancomycin is administered as 500 mg per day or 250 mg per day.
227 . The method of claim 218 , wherein the vancomycin is administered as 4 doses of 125 mg per day or 2 doses of 125 mg per day.
228 . The method of claim 218 , wherein the vancomycin is administered on five consecutive days up to two days prior to the day of administration of the first dose of the pharmaceutical composition, and wherein the method includes a washout day one day prior to the day of administration of the first dose the pharmaceutical composition.
229 . A method for reducing levels of primary bile acids and/or increasing levels of secondary bile acids in a subject, the method comprising:
administering vancomycin to the subject, followed by administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a purified bacterial mixture, wherein the purified bacterial mixture comprises:
(i) a bacterial strain belonging to Clostridium bolteae;
(ii) a bacterial strain belonging to Anaerotruncus colihominis;
(iii) a bacterial strain belonging to Drancourtella massiliensis or Sellimonas intestinalis;
(iv) a bacterial strain belonging to Clostridium symbiosum;
(v) a bacterial strain belonging to Blautia producta;
(vi) a bacterial strain belonging to Dorea longicatena;
(vii) a bacterial strain belonging to Clostridium innocuum ; and
(viii) a bacterial strain belonging to Flavonifractor plautii,
wherein the vancomycin is administered in multiple doses prior to administering the pharmaceutical composition,
wherein the pharmaceutical composition is administered in multiple doses on consecutive days, and
wherein a total of at least 4.0×10 10 colony forming units (CFUs) or at least 1.1×10 11 CFUs of bacteria are administered to the subject.
230 . The method of claim 229 , wherein a total of at least 4.0×10 10 CFUs of bacteria are administered as at least five doses over at least five days.
231 . The method of claim 229 , wherein a total of at least 1.1×10 11 CFUs of bacteria are administered as at least fourteen doses over at least fourteen days.
232 . The method of claim 229 , wherein each of the multiple doses of the pharmaceutical composition comprises at least 8.0×10 9 CFUs.
233 . The method of claim 229 , wherein the vancomycin is administered as 500 mg per day or 250 mg per day.
234 . The method of claim 229 , wherein the vancomycin is administered on five consecutive days up to two days prior to the day of administration of the first dose of the pharmaceutical composition, and wherein the method includes a washout day one day prior to the day of administration of the first dose of the pharmaceutical composition.
235 . A method for reducing levels of primary bile acids and/or increasing levels of secondary bile acids in a subject, the method comprising:
administering vancomycin to the subject, followed by administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a purified bacterial mixture, wherein the purified bacterial mixture comprises:
(i) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 1;
(ii) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 2;
(iii) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 3;
(iv) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 4;
(v) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 5;
(vi) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 6;
(vii) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 7; and
(viii) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 8,
wherein the vancomycin is administered in multiple doses prior to administering the pharmaceutical composition,
wherein the pharmaceutical composition is administered in multiple doses on consecutive days, and
wherein a total of at least 4.0×10 10 colony forming units (CFUs) or at least 1.1×10 11 CFUs of bacteria are administered to the subject.
236 . The method of claim 235 , wherein:
the bacterial strain of (i) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 1;
the bacterial strain of (ii) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 2;
the bacterial strain of (iii) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 3;
the bacterial strain of (iv) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 4;
the bacterial strain of (v) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 5;
the bacterial strain of (vi) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 6;
the bacterial strain of (vii) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 7; and
the bacterial strain of (viii) comprises a 16S rDNA sequence having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 8.
237 . The method of claim 235 , wherein a total of at least 4.0×10 10 CFUs of bacteria are administered.
238 . The method of claim 235 , wherein a total of at least 1.1×10 11 CFUs of bacteria are administered as at least fourteen doses over at least fourteen days.
239 . The method of claim 235 , wherein each of the multiple doses of the pharmaceutical composition comprises at least 8.0×10 9 CFUs.
240 . The method of claim 235 , wherein the vancomycin is administered as 500 mg per day or 250 mg per day.
241 . The method of claim 235 , wherein the vancomycin is administered on five consecutive days up to two days prior to the day of administration of the first dose of the pharmaceutical composition, and wherein the method includes a washout day one day prior to the day of administration of the first dose of the pharmaceutical composition.