Irritable Bowel Syndrome Message Boards | Re: SHAWNERIC Re: WebMD: IBS/Fruct & SOME OTHER ?'s MAINLY ABT. BACTERIAL OVERGROWTH/Tests, etc.

Marnie, I have a great relationship with most of the doctors at the UNC, who help me a lot.

On the d in IBS.

In D predominate IBS there is more serotonin secreted from certain gut cells, that in turn intiate the peristaltic reflex which then overactivates the lower colon to cause d.

There is also something called the gastro-colonic response to food. This is where the stomach singals to the lower intestine, that food is on the way and the colon gets rid of the foods already process to make way for more food. This responce stimulates and overreaction of the lower colon more in IBS then normals.

FYI

They have been working on this for awhile and although this is sponsored by a drug company, it is also being highly research on IBS from many sources.

Researchers Identify Molecular Alterations in Patients With Irritable Bowel Syndrome
New Research Demonstrates Abnormal Serotonin Signaling in IBS
BALTIMORE, MD -- MARKET WIRE -- 10/13/2003 -- Novel research shows that alterations in serotonin signaling in the gastrointestinal GI tract are present in patients with Irritable Bowel Syndrome IBS. These data shed light on the alterations in gut motility, secretion and sensation, as well as the clinical manifestations of IBS that include abdominal discomfort or pain, bloating, constipation and/or diarrhea.

The study findings were presented today by two lead investigators from the University of Vermont, Peter Moses, M.D., associate professor of Medicine and Director of Clinical Research in the Digestive Diseases, and Gary Mawe, Ph.D., professor of anatomy and neurobiology, in an oral presentation during the plenary session at the 68th Annual Scientific Meeting of the American College of Gastroenterology.

"Serotonin is a critical signaling molecule necessary for normal gut function -- when released, it causes gut motility and secretion, and triggers signals to the brain and spinal cord," said Moses. "Our finding that key elements of serotonin signaling are changed in IBS lends credibility to the notion that IBS is not simply a psychological or social disorder as was once thought, but instead is due to altered gut biochemistry and interactions between the gut and the brain."

Serotonin 5-HT is a naturally occurring neurotransmitter and signaling molecule. Ninety-five percent of all serotonin is localized in the GI tract where it plays a key role in the motor, sensory and secretory functions of the gut. For some time, scientists have suspected that alterations in serotonin may contribute to abnormal conditions in the GI tract.

"Now we have a perspective on molecular changes in the intestines of individuals with IBS that we did not have before," said Mawe. "We identified a significant decrease in the serotonin transporter in cells that form the inner lining of the bowel -- the same serotonin transporter that is located in cells in the brain. In the gut, this transporter acts as a sponge to remove serotonin once it is released, and therefore stops its actions. Because the transporter is diminished in IBS, serotonin stays around longer, and this can lead to changes in motility, secretion and sensitivity."

The study examined tissue obtained from 43 healthy controls and 32 patients with IBS and 22 patients with inflammatory bowel disease IBD. IBS patients were defined strictly using ROME II diagnostic criteria. Each biopsy was evaluated by five parameters: immunohistochemical staining, histological assessment, serotonin content, serotonin release and the measurement of mRNA encoding. The study also examined the molecular components of serotonin signaling, including the serotonin re-uptake system. Specifically, the investigators measured serotonin content, the endocrine cell number, serotonin release and presence of serotonin transporters SERT. Serotonin transporters are regulatory molecules that control the activity of serotonin within nerve endings in the GI tract to coordinate motility, visceral sensitivity and intestinal secretion.

In patients with IBS, the study found a significant decrease in serotonin content and significantly higher endocrine cell EC populations in patients with IBS compared to controls, while the release of serotonin from EC cells was not significantly different. In terms of the way the body inactivates serotonin signaling, or the serotonin re-uptake system, SERT mRNA and SERT immunoreactivity were markedly reduced. This reduction led to a decrease in the capacity to remove serotonin from intracellular space once it was released, thus increasing serotonin availability.

The study was sponsored through a research grant from Novartis Pharmaceuticals, maker of Zelnorm� tegaserod maleate for IBS-C. In addition to Moses and Mawe, members of the study team included Matthew Coates, Christine Mahoney, David Linden, Joanna Sampson and Eric Newton of the University of Vermont; Michael Gershon and Jason Chen of the Department of Anatomy and Cell Biology at Columbia University; Keith Sharkey of the Department of Physiology and Biophysics at the University of Calgary, and Michael Crowell of the Clinical Research Department at Novartis Pharmaceuticals.

Jennifer Nachbur
802 656-7875
jennifer.nachbur@uvm.edu

ONSITE
ACG: Michael Szumera
917 689-3392

www.marketwire.com/mw/rel...e_id=58540

"Ask The Expert
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Image of a cadeusus
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General Medical Questions
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Q: I have suffered from irritable-bowel syndrome for many years. I get diarrhea. The doctors I've seen have offered little help. Recently, my daughter suggested I try an over-the-counter medicine called "5-Hydroxy-tryptophan," made by a company called Natrol Inc. My daughter says it is a mild antidepressant. It seems to have helped quite a bit, but it also seems to slow me down and make me feel tired. Can you give me any information on this? What is it, exactly, and are there any serious side effects? The only other medicine I take is Synthroid.
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The Trusted Source
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Harold J. DeMonaco, M.S.

Harold J. DeMonaco, M.S., is senior analyst, Innovative Diagnostics and Therapeutics, and the chair of the Human Research Committee at the Massachusetts General Hospital. He is author of over 20 publications in the pharmacy and medical literature and routinely reviews manuscript submissions for eight medical journals.
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June 19, 2001
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A:

Irritable bowel syndrome is now recognized as a disorder of serotonin activity. Serotonin is a neurotransmitter in the brain that regulates sleep, mood depression, anxiety, aggression, appetite, temperature, sexual behavior and pain sensation. Serotonin also acts as a neurotransmitter in the gastrointestinal tract.

Excessive serotonin activity in the gastrointestinal system enteric nervous system is thought to cause the diarrhea of irritable-bowel syndrome. The enteric nervous system detects bowel distension expansion on the basis of pressure-sensitive cells in the bowel lumen opening. Once activated, these pressure-sensitive cells promote the release of serotonin, which in turn promotes both secretory function and peristaltic function the contractions of the intestines that force the contents outward. At least four serotonergic receptors have been identified to be participants in the secretory and peristaltic response.

Patients with diarrhea-predominant IBS may have higher levels of serotonin after eating than do people without the disorder. This recognition led to the development of the first drug used specifically to treat diarrheal symptoms of IBS, alosetron also known as Lotronex. Alosetron blocked the specific serotonin receptors responsible for recognizing bowel distention. In doing so, it blocked the effects of serotonin and reduced both bowel secretions and peristalsis. Constipation was the most common side effect seen. Note: Alosetron was removed from the market by the manufacturer after repeated reports of a dangerous condition known as ischemic colitis became known. Tegaserod Zelmac is another drug under development and under review by the U.S. Food and Drug Administration for approval. Tegaserod is indicated for the treatment of constipation-predominant IBS and works to increase enteric nervous system serotonin activity.

So, increasing serotonin activity in the enteric nervous system produces increased bowel secretions and peristalsis and potentially diarrhea, whereas depressing serotonin activity produces reduced secretions and reduce peristalsis and potentially constipation. Increasing serotonin activity in the brain would increase awareness and, in higher doses, produce anxiety, insomnia and restlessness. So I would have expected exactly the opposite effects of those that you experienced.

I am unable to identify any possible drug interactions between 5-HTP and Synthroid levothyroxine but the symptoms described suggest a check with your doctor may be in order. Persistent feelings of tiredness and constipation may be signs of an underactive thyroid hypothyroidism.

June 19, 2001

This one is from Medscape and part of the above study.

"FYI

Pathophysiology
Altered Serotonin Signaling?
The pathogenesis of IBS remains obscure, and in particular, an explanation for alternating diarrhea and constipation has been elusive. In arguably one of the most important papers presented during this year's meeting, Moses and colleagues21 studied potential deregulation of the gut's serotonin transporter in IBS.

It is known that serotonin 5-hydroxytryptamine or 5HT is released from enteroendocrine or enterochromaffin cells in response to either chemical or mechanical stimulation of the gut mucosa. Serotonin in turn initiates peristalsis, and then the serotonin released is taken up in health by a highly selective serotonin transporter SERT. One potential mechanism that could explain altered bowel function in IBS is an abnormality in the serotonin transporter itself. The study authors evaluated this hypothesis in patients with IBS with constipation and IBS with diarrhea compared with patients with ulcerative colitis and healthy controls. They were able to convincing show on blinded review that SERT immunoreactivity was less intense in patients with IBS with constipation and patients with ulcerative colitis.

If these findings are indeed correct, they represent a landmark observation. The findings suggest that patients with constipation and IBS may have a reduced capacity to reuptake serotonin, leading to excess free serotonin and then desensitization of these receptors, thus reducing motor function. In contrast, in the setting of diarrhea, serotonin uptake was normal. If the underlying abnormality in serotonin transporter function alternated, then this would in turn explain alternating constipation and diarrhea.

These data strongly suggest that IBS is a "real" gut disease and a potential diagnostic disease marker. They also suggest that it is valid to subdivide IBS into constipation and diarrhea symptom subgroups. This study also provides additional rationale for the use of serotonin-modulating agents in IBS and provides a new target for drug modulation. Confirmation of these very exciting initial findings in larger patient samples is awaited with great interest."

But Dr Drossman wrote this for me at the end of the foods comments.

This is where the latest IBS research stands really.

"The cause of IBS is yet to be determined. However, modern research understands IBS as a disorder of increased reactivity of the bowel, visceral hypersensitivity and dysfunction of the brain-but axis. There are subgroups being defined as well, including post-infectious IBS which can lead to IBS symptoms. Other work using brain imaging shows that the pain regulation center of the brain cingulate cortex can be impaired, as well as good evidence for there being abnormalities in motility which can at least in part explain the diarrhea and constipation. So finding a specific "cause" of IBS has grown out of general interest in place of understanding physiological subgroups that may become amenable to more specific treatments. Hope that helps."
Doug

www.ibshealth.com/ibs_foods_2.htm

Hope this helps some, its not the whole picture, but may play a major role on the motility symptoms of d and c and d/c in IBS. As well as help to explain in part some other issues in IBS.

If you do a search on serotonin and IBS, there is a ton of info on it all.

On lactose intolerence, its worth getting tested and perhaps for fructose as well. The hydrogen test is more for the condition of Small Bowel Bacterial overgrowth, not IBS.

C-diff, I believe shows up in stool testing, the stool testing is a gi test, that most doctors and gi specialists do.

Hope this helps I will take a look some more at you other post and see, but have to work all day today.

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My website on IBS is www.ibshealth.com

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