Methods of diagnosis, selection, and treatment of diseases and conditions caused by or associated with methanogens

Abstract

The invention described herein provides for methods and systems for determining, selecting, and/or treating diseases and conditions caused by or associated with high quantities of methanogens in a subject, or diseases and conditions caused by or associated with low quantities of methanogens in a subject. In various embodiments, a therapy to inhibit the growth of methanogens or to promote the growth of methanogens are selected and/or administered to a subject in need thereof.

1 . A method of treating a subject who has or is suspected to have a disease or condition caused by or associated with having a high methanogen quantity or a disease or condition caused by or associated with having a low methanogen quantity, comprising:
 administering a first therapy to the subject who has or is determined to have a methanogen quantity that is higher than a reference value based on the recognition that the first therapy is appropriate for subjects who have a methanogen quantity higher than the reference value, or   administering a second therapy to the subject who has or is determined to have a methanogen quantity lower than a reference value based on the recognition that the second therapy is appropriate for subjects who have a methanogen quantity lower than the reference value.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the subject has been determined to have a high quantity of methanogens. 
     
     
         4 . The method of  claim 1 , wherein the subject has been determined to have a low quantity of methanogens. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the disease or condition caused by or associated with having the high methanogen quantity is selected from the group consisting of obesity, constipation, fatty liver (NASH), pre-diabetes, diabetes, type II diabetes, insulin resistance, glucose intolerance, hyperglycemia, and combinations thereof. 
     
     
         10 . The method of  claim 1 , wherein disease or condition caused by or associated with having the high methanogen quantity is hyperlipidemia or high cholesterol. 
     
     
         11 . The method of  claim 1 , wherein the disease or condition caused by or associated with having the low methanogen quantity is Crohn's disease, ulcerative colitis, microscopic colitis, malnutrition, malabsorption, or refeeding syndrome. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the first therapy is an antibiotic or a combination of two or more antibiotics. 
     
     
         15 . The method of  claim 14 , wherein the antibiotic or the combination of two or more antibiotics is selected from the group consisting of rifaximin, neomycin, vancomycin, and metronidazole. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         21 - 205 . (canceled) 
     
     
         206 . A method, comprising
 subjecting a biological sample from a subject to analysis for methanogen quantity;   comparing the methanogen quantity to a reference value; and   selecting or directing a first therapy for the subject if the methanogen quantity is higher than the reference value based on the recognition that the first therapy is appropriate for subjects who have a methanogen quantity higher than the reference value, or   selecting or directing a second therapy for the subject if the methanogen quantity is lower than the reference value based on the recognition that the second therapy is appropriate for subjects who have a methanogen quantity lower than the reference value,   wherein the subject has or is suspected to have a disease or condition caused by or associated with having a high methanogen quantity or a disease or condition caused by or associated with having a low methanogen quantity.   
     
     
         207 . The method of  claim 206 , further comprising administering the selected or directed therapy. 
     
     
         208 . The method of  claim 206 , wherein the biological sample is selected from stool, mucosal biopsy from a site in the gastrointestinal tract, aspirated liquid from a site in the gastrointestinal tract, or combinations thereof. 
     
     
         209 . The method of  claim 206 , wherein the analysis for methanogen quantity is by using quantitative polymerase chain reaction (qPCR). 
     
     
         210 . The method of  claim 206 ,
 wherein the disease or condition caused by or associated with having the high methanogen quantity is selected from the group consisting of obesity, constipation, fatty liver (NASH), pre-diabetes, diabetes, type II diabetes, insulin resistance, glucose intolerance, hyperglycemia, and combinations thereof; or   wherein disease or condition caused by or associated with having the high methanogen quantity is hyperlipidemia or high cholesterol; or   wherein the disease or condition caused by or associated with having the low methanogen quantity is Crohn's disease, ulcerative colitis, microscopic colitis, malnutrition, malabsorption, or refeeding syndrome.   
     
     
         211 . The method of  claim 206 , wherein the reference value is about 1,000 per ml of the biological sample. 
     
     
         212 . The method of  claim 206 , wherein the first therapy is an antibiotic or a combination of two or more antibiotics. 
     
     
         213 . The method of  claim 206 , wherein the first therapy is a statin. 
     
     
         214 . The method of  claim 206 ,
 wherein the disease or condition is obesity and the first therapy is an anti-obesity drug; or   wherein the disease or a condition is selected from the group consisting of pre-diabetes, diabetes, type II diabetes, insulin resistance, glucose intolerance, hyperglycemia, the first therapy is selected from the group consisting of alpha-glucosidase inhibitors, amylin analog, dipeptidyl peptidase-4 inhibitor, GLP1 agonist, meglitinide, sulfonylurea, biguanide, thiazolidinedione (TZD), insulin, and combinations thereof; or   wherein the disease or a condition is selected from the group consisting of pre-diabetes, diabetes, type II diabetes, insulin resistance, glucose intolerance, hyperglycemia, the first therapy is selected from the group consisting Glipizide/Metformin, Glyburide/Metformin, Pioglitazone/Glimepiride, Pioglitazone/Metformin, Repaglinide/Metformin, Rosiglitazone/Glimepiride, Rosiglitazone/Metformin, Saxagliptin/Metformin, Sitagliptin/Simvastatin, Sitagliptin/Metformin, Linagliptin/Metformin, Alogliptin/Metformin, Alogliptin/Pioglitazone, bromocriptine, welchol, and combinations thereof; or   wherein the disease or condition is constipation, and the first therapy is selected from the group consisting of laxative, diet, guanylate cyclase C agonist, a serotonin agonist, a chloride channel agonist and combinations thereof; or   wherein the disease or condition is fatty liver, and the first therapy is metformin; or   wherein the disease or condition is Crohn's disease, ulcerative colitis, microscopic colitis, malnutrition, malabsorption, or refeeding syndrome and the second therapy is administering a methanogen.   
     
     
         215 . A method, comprising
 subjecting a breath sample from a subject to analysis for methane quantity and hydrogen quantity;   comparing the methane quantity and hydrogen quantity to a methane reference value and a hydrogen reference value; and   selecting or directing a first therapy for the subject if the methane quantity is higher than the methane reference value and the hydrogen quantity at or before 90 minutes during a breath test is higher than the hydrogen reference value based on the recognition that the first therapy is appropriate for subjects who have a methane quantity and hydrogen quantity higher than the methane reference value and the hydrogen reference value, or   selecting or directing a second therapy for the subject if the methane quantity and hydrogen quantity is lower than the methane reference value and the hydrogen reference value based on the recognition that the second therapy is appropriate for subjects who have a methane quantity and hydrogen quantity lower than the methane reference value and the hydrogen reference value,   wherein the subject has or is suspected to have a disease or condition caused by or associated with having a high methanogen quantity or a disease or condition caused by or associated with having a low methanogen quantity.   
     
     
         216 . The method of  claim 215 , further comprising administering the selected or directed therapy. 
     
     
         217 . The method of  claim 215 , wherein the methane reference value is about 3 ppm and the hydrogen reference value is about 20 ppm.