Gut
Mast cells in the lining of the digestive tract can release histamine in response to stress, certain foods, or environmental triggers—leading to symptoms like bloating, cramping, diarrhea, constipation, and nausea.
In some individuals, these reactions are misdiagnosed as classic IBS, when in fact histamine intolerance or mast cell activation may be the root cause. The overlap between histamine-related gut dysfunction and IBS highlights the need for a more nuanced, personalized approach to digestive symptoms—especially when conventional treatments fall short.
Irritable Bowel Syndrome
What is the connection between IBS and Histamine?
We’re supposed to be in tune with our gut feelings. What happens when our gut gets too into its feelings? We call this, IBS, and histamine really puts the Irritable in this BS.
How?
Mast cells, brimming with histamine, can be found everywhere throughout our intestines. Normally they manage how we digest, the flow of poop and the chit chat between the nerves in our gut. Histamine, in healthy amounts, keeps the peace between our gut and brain.
When mast cells get out of hand, they multiply and buzz, get closer to and annoy the nerves in the gut wall. People with IBS are already sensitive as a baseline. Imagine when mast cells break open and let loose too many of their toxic contents, there’s no hope for the gentle gut. Normal motility is either sped up or slowed right down. The protective juices that line our digestive tract dry right up.
We bloat, we stall, we hurt.
An irritated gut needs better communication between its own nerves. Soothing angry mast cells is one very helpful way to get the gut to stop fuming. Histamine blockers specific to the digestive tract are one way to do just that.
In a study of 20 refractory IBS patients, 19 had MC symptoms and 11 of 12 studied for MC mediators had positive results.
Sign up for our courses to learn how to mindfully treat mast cell IBS.
Inflammatory Bowel Disease
Inflammatory bowel diseases are Crohn’s and Colitis. These are systemic autoimmune conditions that aren’t directly linked to histamine, but there are some interesting connections worth exploring.
People with IBD produce less DAO (Diamine Oxidase) so they cannot break down histamine, a major player in inflammation.
Histamine is released by mast cells and influenced by gut microbes, and levels are often elevated in inflamed intestinal tissue. In IBD, chronic inflammation may reduce levels of diamine oxidase (DAO), potentially leading to histamine intolerance—causing symptoms like bloating, diarrhea, and abdominal pain that mimic or worsen IBD flares. While not a root cause, histamine may amplify gut immune responses and contribute to disease severity in some individuals, making it a worthwhile area for adjunctive support through diet, DAO supplements, or mast cell stabilizers.
We use mast cell stabilizers a lot in IBD with good success.
Small Intestinal Bacterial Overgrowth
Why would a person with a histamine problem develop bloating and diarrhea?
Because histamine can cause an overgrowth of bacteria in their small intestine. Small intestinal bacterial overgrowth (SIBO) was shown to be common in MCAS. Bacterial overgrowth was present in 31% of MCAS patients, when only 10% of the general population had it.
SIBO probably comes from the altered motility of the intestines. Histamine can damage nerve cells called glial cells affecting the motor control of the intestines or by abnormal immunity or even by making the nerves themselves not communicate properly. This crossed-talk can disrupt the normal rhythm of gut flow. This is how SIBO explains diarrhea and bloating in some MCAS sufferers. The effect of other chemicals in mast cells, called mediators, on the GI tract likely explains the rest of the problems that can arise.
SIBO itself then stimulates even more mast cells to activate, creating a vicious cycle that reinforces more bloating, often unrelated to when you ate your last histaminy meal.
