# Rifaximin dose-finding study for the treatment of SIBO



## Nanobug (Nov 7, 2006)

Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth.


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## Moises (May 20, 2000)

Nanobug you and Kathleen M have made clear to me a distinction which I was not consistently making: digestion and absorption are different processes. "Digestion" is defined as breaking a substance down to its fundamental nutritional elements: monosachharides, amino acids, etc. "Absorption" is defined as the process whereby a substance passes through the microvilli into the bloodstream.Gottschall's underlying assumption is, That which is digested will be absorbed. Pimentel's book does not explicitly address this. But he appears to make this assumption implicitly. His numerous discussions of the elemental diet argue that digested foods will be absorbed, leaving no residue for the small bowel bacteria, consequently starving them and curing the IBS. The assumption is that if the food is digested, it will be absorbed. I mention this all as preamble to a comment on the study you posted. In this study glucose was used in the breath test. Glucose is already digested. That is why Pimentel opposes the use of glucose breath tests, because he assumes digestion implies absorption. Yet this study demonstrated a rifaximin dose dependent hydrogen effect. This study suggests that the assumption that digestion implies absorption is false. Kathleen M's comments regarding Pimentel's dietary recommendations suggest a more complex assumption: digested substances of _x_ grams or less will be absorbed and digested substances greater than _x_ grams will not be absorbed. If this assumption were confirmed, it would explain the efficacy of glucose breath tests.What does the test that you have cited demonstrate? If you give subjects 50 gms of glucose (about the carbohydrate content of 4 slices of breaad) small intestinal bacteria will be fed. If you give subjects with small intestinal bacteria rifaximin, those bacteria will be killed in proportion to the amount of rifaximin.So the group of subjects who receive the most rifaximin showed the biggest drop in hydrogen exhalation. It seems to me that two explanations are possible:1. Eradication of bacteria increased the absorption of the glucose.2. Eradication of the bacteria left the absorption of the glucose the same but the hydrogen exhalation dropped because there were no bacteria to metabolize the glucose.I think that there would be an easy method to test whether 1 or 2 is the better explanation. First, do a breath test and note the height of the hydrogen peaks for both the small and large intestine. There should be a peak when the small intestinal bacteria metabolize the glucose and another peak when the colonic bacteria metabolize the glucose. Then do the course of rifaximin and wait sufficient time for the colonic bacteria to recolonize. Now do another breath test. In "cured" patients there should only be one peak, when the glucose hits the colon. If hypothesis 1, above, is correct, then there should be more glucose absorbed in the small bowel, leaving less glucose available for the large bowel's bacteria to eat. So the colonic hydrogen peak after rifaximin should be lower than it was prior to the hydrogen trial. If 2 were correct, the colonic hydrogen peak would be the same after the rifaximin trial as it was before.


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## Nanobug (Nov 7, 2006)

> quote:digested substances of x grams or less will be absorbed and digested substances greater than x grams will not be absorbed.


My limited understanding of the subject matter is that the intestine has a finite ability to transport nutrients through its walls. The maximum rate at which nutrients are absorbed varies from person to person and from type of nutrient to type of nutrient. I don't know what these limits typically are in healthy people although I suspect that these could be very low in people with certain gastrointestinal diseases, the obvious example being malabsorption.


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## Kathleen M. (Nov 16, 1999)

Well I am making the assumption you dump enough glucose in because it is the same 1 peak vs 2 peak evaluation and if all of it is totally absorbed in all people then everyone would have no peaks.Almost any system in the body can be saturated out. For instance your body normally completely and safely disposes of the very minor but toxic metabolite of Tylenol. However, if you take enough Tylenol you overwhelm the clean up system and die of liver failure pretty quickly. If you drink a lot so you make more of the toxic metabolit than usual you can also damage your liver. Even though the system in place that cleans it up safely works very well, you can through a couple of mechanisms (and there may be more than these two) get around that if you work at it hard enough. At normal doses in people that don't drink heavily it is really a very safe drug, you do something to overwhelm the system and you run into trouble. Whenever there are competing tests people have their reasons for why they prefer one over the other, and sometimes there is a lot of data and sometimes there is more of a gut feeling.I'll see if I can find the glucose vs lactulose study for breath tests I read....hold on...Found this http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsum is one where they do both and compare to aspirates. It is a bit newer than the paper I was thinking of (as I went looking around the time Pimental started publishing on this) And they are looking at more traditional SIBO patients.I haven't seen it used in a lot of practices, but the Xylose test here seems better than either glucose or lactulose. http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsumOf course mos people think the aspirates are still better than breath tests but it sounds Pimental disagrees http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsumHere is one where they looked at fermentation vs absorption of glucose, but I'd have to do more reading to really get a full understanding of it. http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsumUnfortunately with all these tests you find quite a few papers touting how great any given test is and those that talk about how it is totally inadequate.What would be great is a large comprehensive test with all sorts of people (classic SIBO, IBS SIBO, normal controls, other assorted GI disorders and significant numbers of all of them) who are tested multiple ways and really well compared.I don't know that anyone is going to pay for that. It would end up costing a lot.K.


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