INSULIN-SENSITIZING AGENT AND BUTYRATE-PRODUCING BACTERIUM
This disclosure is concerned with a combination comprising at least one butyrate-producing bacterium and at least one insulin-sensitizing agent for use in the prevention and/or treatment of metabolic disease, insulin resistance and insulin resistance-related conditions, preferably chosen from type 1 diabetes mellitus, type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, insulin resistance in endocrine disease, Polycystic Ovary Syndrome (PCOS), Nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). The insulin-sensitizing agent and the butyrate-producing bacterium, at least in part, have a synergistic effect on lowering insulin resistance in subjects.
1 . A method of preventing and/or treating insulin resistance and/or insulin resistance-related conditions in a subject, the method comprising administering to the subject an insulin-sensitizing agent selected from the group consisting of
chromium;
inositol;
metformin; and
sorbitol
wherein the insulin-sensitizing agent is combined with a butyrate-producing bacterium selected from the group consisting of
Anaerobutyricum soehngenii or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO: 1 or SEQ ID NO:2;
Intestinimonas butyriciproducens or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:3; and
Anaerostipes rhamnosivorans or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:4,
wherein the butyrate-producing bacterium is micro-encapsulated when
the insulin-sensitizing agent is metformin and the butyrate-producing bacterium is Anaerobutyricum soehngenii or a relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO: 1 or SEQ ID NO:2; or
the insulin-sensitizing agent is chromium or inositol and the butyrate-producing bacterium is Intestinimonas butyriciproducens or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:3 or Anaerostipes rhamnosivorans or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO:4.
2 . The method according to claim 1 , wherein the butyrate-producing bacterium is micro-encapsulated.
3 . The method according to claim 1 , wherein the insulin resistance-related condition is selected from the group consisting of metabolic syndrome, type 1 diabetes mellitus, type 2 diabetes mellitus, dyslipidemia, insulin resistance in endocrine disease, Polycystic Ovary Syndrome (PCOS), Nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and a combination of any thereof.
4 . The method according to claim 1 , wherein the insulin-sensitizing agent is chromium, and the butyrate-producing bacterium is Anaerobutyricum soehngenii or relative thereof having a 16S rRNA gene sequence with at least 97% sequence identity with SEQ ID NO: 1 or SEQ ID NO:2.
5 . The method according to claim 1 , wherein the chromium is chromium(III) picolinate.
6 . The method according to claim 1 , wherein the butyrate-producing bacterium is administered separately, sequentially or simultaneously to the insulin-sensitizing agent.
7 . The method according to claim 1 , wherein the butyrate-producing bacterium is present in an amount ranging from 10 4 to 10 15 colony forming units (CFU).
8 . The method according to claim 1 , wherein the butyrate-producing bacterium is present in lyophilized form.
9 . The method according to claim 1 , wherein metformin is present in an amount ranging from 100 mg to 5000 mg.
10 . The method according to claim 1 , wherein chromium is present in an amount ranging from 10 μg to 5000 μg.
11 . The method according to claim 1 , wherein inositol is present in an amount ranging from 10 mg to 100 g.
12 . The method according any one of the preceding claims , wherein the insulin-sensitizing agent and the butyrate-producing bacterium are comprised in a composition.
13 . The method according to claim 12 wherein the composition comprises a physiologically acceptable carrier.
14 . The method according to claim 12 , wherein the composition is a pharmaceutical composition, a solid dosage form, a capsule, a tablet, or a powder.
15 . The method according to claim 12 , wherein the composition is a food composition, preferably a dairy product, a fermented dairy product, a yogurt or a yogurt drink.