Shanti1
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Clinical studies support the hypothesis that histamine is an inciting factor in IBS for a sizable cohort.
Antihistamine reduces pain in irritable bowel syndrome
In a 12-week randomised trial, the team gave 28 patients the H1 antihistamine ebastine and 27 patients a placebo. Ebastine treatment significantly reduced the mean pain score, while no change was observed in the placebo group. Nearly half of ebastine-treated patients reported considerable symptom relief.
Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patient
Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones.
Gut Microbes that Release Histamine Worsen IBS Pain
In this study, patients were assessed over several months. High levels of histamine were found in fecal samples when patients were also feeling severe pain, and when they were free of pain, histamine levels in stool were low, revealed senior study author and gastroenterologist Premysl Bercik, a professor at McMaster.
The researchers also colonized mice that had no gut microbiota with gut microbes from IBS patients. Control mice were colonized with gut microbes from healthy human volunteers. With this model, the scientists determined that K. aerogenes converts an amino acid called histidine, which is found in the diet, into histamine, which is known to be involved in pain signaling. The immune system in the gut is also activated by that bacterially converted histamine, where the histamine-4 receptor binds to it, attracting mast cells. The mast cells can can trigger additional inflammation and pain by producing more histamine and other molecules.
"Now that we know how the histamine is produced in the gut, we can identify and develop therapies that target the histamine producing bacteria," said first study author Giada de Palma, an assistant professor at McMaster.
If mice that had been exposed to K. aerogenes were given a diet with low levels of fermentable carbohydrates (sometimes known as a low FODMAP diet), the production of histamine was significantly reduced. There were changes in acidity and fermentation by bacteria in the gut, inhibiting an enzyme that generates the bacterial histamine.
This work has shown why diets that are low in fermentable carbohydrates are helpful for IBS patients, who are known to carry abnormally high levels of mast cells in their gastrointestinal tracts. Treatments that target mast cells or histamine may, therefore, be beneficial as well.
"Although mast cell treatment in IBS has been explored, a novel approach based on our research would be targeting the bacterial histamine production or H4R pathways," Bercik said.
"Many, but not all IBS patients, will benefit from therapies targeting this histamine driven pathway," noted co-first study author David Reed, an assistant professor at Queen's. Biomarkers might be helpful to identify the patients that would probably respond to the treatment, added Reed.
Sources: McMaster University, Science Translational Medicine
(Note: Title of thread edited from Histamine as an inciting factor in IBS to current title for clarity)
Antihistamine reduces pain in irritable bowel syndrome
In a 12-week randomised trial, the team gave 28 patients the H1 antihistamine ebastine and 27 patients a placebo. Ebastine treatment significantly reduced the mean pain score, while no change was observed in the placebo group. Nearly half of ebastine-treated patients reported considerable symptom relief.
Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patient
Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones.
Gut Microbes that Release Histamine Worsen IBS Pain
In this study, patients were assessed over several months. High levels of histamine were found in fecal samples when patients were also feeling severe pain, and when they were free of pain, histamine levels in stool were low, revealed senior study author and gastroenterologist Premysl Bercik, a professor at McMaster.
The researchers also colonized mice that had no gut microbiota with gut microbes from IBS patients. Control mice were colonized with gut microbes from healthy human volunteers. With this model, the scientists determined that K. aerogenes converts an amino acid called histidine, which is found in the diet, into histamine, which is known to be involved in pain signaling. The immune system in the gut is also activated by that bacterially converted histamine, where the histamine-4 receptor binds to it, attracting mast cells. The mast cells can can trigger additional inflammation and pain by producing more histamine and other molecules.
"Now that we know how the histamine is produced in the gut, we can identify and develop therapies that target the histamine producing bacteria," said first study author Giada de Palma, an assistant professor at McMaster.
If mice that had been exposed to K. aerogenes were given a diet with low levels of fermentable carbohydrates (sometimes known as a low FODMAP diet), the production of histamine was significantly reduced. There were changes in acidity and fermentation by bacteria in the gut, inhibiting an enzyme that generates the bacterial histamine.
This work has shown why diets that are low in fermentable carbohydrates are helpful for IBS patients, who are known to carry abnormally high levels of mast cells in their gastrointestinal tracts. Treatments that target mast cells or histamine may, therefore, be beneficial as well.
"Although mast cell treatment in IBS has been explored, a novel approach based on our research would be targeting the bacterial histamine production or H4R pathways," Bercik said.
"Many, but not all IBS patients, will benefit from therapies targeting this histamine driven pathway," noted co-first study author David Reed, an assistant professor at Queen's. Biomarkers might be helpful to identify the patients that would probably respond to the treatment, added Reed.
Sources: McMaster University, Science Translational Medicine
(Note: Title of thread edited from Histamine as an inciting factor in IBS to current title for clarity)
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