Manipulation of the rate of gastrointestinal transit by modulating intestinal methane concertration

Abstract

Disclosed is a method of manipulating the rate of gastrointestinal transit in a mammalian subject Also disclosed is the use, in the manufacture of a medicamens for the treatment of constipation, of a selective inhibitor of methanogensis, a methanogen-displacing probiotic agent, or a prebiotic agent that inhibits the growth of methanogenic bacteria or promotes the growth of competing non-methanogenic intestinal flora. Alternatively, in accordance with the invention, is disclosed the use in the manufacture of a medicament for the treatment of diarrhea, of methane, or a methane precursor, a methanogenic or other methane-enhancing probiotic agent, or a methanogenesis-enhancing prebiotic agent.

Description

BACKGROUND OF THE INVENTION Discussion of the Related Art [0001] Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen in more than 15% of the population (1,2). [0002] Over the last few years, progress has been made in characterizing irritable bowel syndrome (IBS). Studies have demonstrated altered gut motility (3), peripheral (4) and central (5) sensory dysfunction, as well as an exaggerated response to stress (6) in this syndrome. However, there is no finding that can be identified in a majority of patients and by extension, there is no diagnostic test that is associated with IBS. As a result, investigators have created complex diagnostic schema such as the Rome criteria to help diagnose and categorize the syndrome (7,8). [0003] One consistent clinical finding in IBS is gas in combination with bloating and visible distention (9,10). Koide et al. recently found small intestinal gas to be significantly increased in IBS compared to controls (11) regardless of whet...

AI Technical Summary

Benefits of technology

[0012] The present invention relates to a method of manipulating the rate of gastrointestinal transit in a mammalian subject, including a human patient. The method involves: (a) increasing the rate of gastrointestinal transit by causing the partial pressure of methane in the subject's intestines to be decreased; and (b) decreasing the rate of gastrointestinal transit by causing the partial pressure of methane in the subject's intestines, for example in the distal gut, to be increased.

[0013] Thus, by practicing the inventive method to increase the rate of gastrointestinal transit, constipation and disorders exhibiting constipation can be treated in subjects in whom abnormally elevated intestinal methane levels are detectable (e.g., in cases of constipation-predominant irritable bowel syndrome [IBS], pseudoobstruction, colonic inertia, postoperative ileus, encopresis, hepatic encephalopathy, or medication-induced constipation). In accordance with this embodiment of the present invention, the partial pressure of methane in the subject's intestines can be decreased by administering to the subject's intestinal lumen a selective inhibitor of methanogenesis, such as monensin, or a methanogen-displacing probiotic agent, or a prebiotic agent that inhibits the growth of methanogenic bacteria or promotes the growth of competing non-methanogenic intestinal flora.

[0015] And alternatively, by practicing the inventive method to decrease the rate of gastrointestinal transit, patients with diarrhea and disorders exhibiting diarrhea can be treated (e.g., cases of diarrhea-predominant IBS, Crohn's disease, ulcerative colitis, celiac disease, microscopic colitis, dumping syndrome, rapid transit, short bowel syndrome, post-gastrectomy syndrome, diabetic diarrhea, hyperemesis, or antibiotic-associated diarrhea). In accordance with this embodiment of the present invention, the partial pressure of methane in the subject's intestines can be increased by administering methane gas to the intestinal lumen of the subject, for example into the distal segment of the intestine of the subject, or by administering to the subject a methanogenic probiotic agent or methogenesis-enhancing prebiotic agent.

Problems solved by technology

However, there is no finding that can be identified in a majority of patients and by extension, there is no diagnostic test that is associated with IBS.

The main issue with culture is accessibility.

Riordan, et al. compared breath testing to direct culture and found the breath test to lack reliability (29).

As such, direct culture is only practical in the patient whose SIBO is so severe that the bacteria has expanded proximally into the duodenum or proximal jejunum.

Until recently, gas studies in IBS have been limited to the investigation of flatus.

Yet, even these studies suggest the presence of excessive bacteria in IBS.

However, the contrasting diarrhea and constipation predominant subgroups in IBS remain unexplained.

Images