SIBO - Small Intestinal Bacterial Overgrowth

What is SIBO? What is the difference between SIBO and gut dysbiosis? How to diagnose SIBO? What is the best treatment for SIBO? Are SIBO treatments safe and effective?

What is SIBO?

SIBO review (2007) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099351/

Small intestinal bacterial overgrowth (SIBO) is defined as the presence of excessive bacteria in the small intestine. SIBO is frequently implicated as the cause of chronic diarrhea and malabsorption. Patients with SIBO may also suffer from unintentional weight loss, nutritional deficiencies, and osteoporosis.

Symptoms of SIBO are nonspecific and include bloating, abdominal distension, abdominal pain or discomfort, diarrhea, fatigue, flatulence, and weakness.

The nonspecific nature of these complaints makes SIBO difficult to distinguish clinically from other disease entities, such as IBS, lactose intolerance, or fructose intolerance. No study has evaluated the specificity of these symptoms; therefore, objective testing is recommended.

The diagnosis of SIBO is controversial.

The mainstay of treatment for SIBO remains antibiotic therapy.

A variety of antibiotics have been used in the treatment of SIBO, most with little supporting evidence.

Attempts at treating SIBO with probiotics (non-pathogenic strains of bacteria) have shown mixed results.

Now from https://en.wikipedia.org/wiki/Small_intestinal_bacterial_overgrowth

Unlike the colon (or large bowel), which is rich with bacteria, the small bowel usually has fewer than 10,000 organisms per millilitre.

The diagnosis of bacterial overgrowth is made by a number of techniques, with the gold standard being an aspirate from the jejunum that grows in excess of 105 bacteria per millilitre.

Small bowel bacterial overgrowth syndrome is treated with an elemental diet or antibiotics, which may be given in a cyclic fashion to prevent tolerance to the antibiotics, sometimes followed by prokinetic drugs to prevent recurrence if dysmotility is a suspected cause.

Bacterial overgrowth can cause a variety of symptoms, many of which are also found in other conditions, making the diagnosis challenging at times.[1][3] Many of the symptoms are due to malabsorption of nutrients due to the effects of bacteria which either metabolize nutrients or cause inflammation of the small bowel, impairing absorption. The symptoms of bacterial overgrowth include nausea, flatus,[4] constipation,[5] bloating, abdominal distension, abdominal pain or discomfort, diarrhea, fatigue, and weakness.[6] SIBO also causes an increased permeability of the small intestine.[7] Some patients may lose weight. Children with bacterial overgrowth may develop malnutrition and have difficulty attaining proper growth. Steatorrhea, a sticky type of diarrhea where fats are not properly absorbed and spill into the stool, may also occur.[4]

Inaccuracy of diagnostic testing for SIBO:

Use and abuse of hydrogen breath tests (2006): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856094/

The Lactulose Breath Test for Diagnosing SIBO in IBS Patients: Another Nail in the Coffin (2008): http://dx.doi.org/10.1111/j.1572-0241.2008.01798.x "test does not discriminate between IBS patients and healthy controls when criteria from recent clinical IBS studies are applied"

The clinical value of breath hydrogen testing (2017): Breath testing is unreliable: http://onlinelibrary.wiley.com/doi/10.1111/jgh.13689/full

Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus (2017): https://www.nature.com/ajg/journal/v112/n5/pdf/ajg201746a.pdf "there is significant heterogeneity in test performance".

Does a glucose‐based hydrogen and methane breath test detect bacterial overgrowth in the jejunum? (2018): https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.13350 "The glucose‐based hydrogen and methane breath test is not sensitive to the overgrowth of jejunal bacteria. However, a positive breath test may indicate altered jejunal function and microbial dysbiosis"

Is the term SIBO based on an incorrect understanding of the gut microbiome?

A microbiota-centric view of diseases of the upper gastrointestinal tract. The distinctive anatomy and physiology of the upper gastrointestinal tract and the difficulty of obtaining samples led to the theory that it was bacteria free. Multiomics studies are indicating otherwise. [review, 2017] http://www.sciencedirect.com/science/article/pii/S246812531630108X

This May 2019 study https://www.nature.com/articles/s41467-019-09964-7 showed that "SIBO based on duodenal aspirate culture does not correspond with patient symptoms, but composition is significantly altered in symptomatic patients"

FMT: The data https://humanmicrobiome.info/fmt#sibo shows that you can take large intestine microbes and put them into the small intestine without problems as long as the donor is healthy/high quality enough. And you can induce "SIBO symptoms" via colon-only FMT if you have a low quality donor. And newer studies have even shown you can treat "SIBO" with FMT.

So "SIBO" doesn't seem differentiable from colon dysbiosis. Pretty much any form of dysbiosis is an overgrowth of some problematic microbes - this recent study on pancreatic cancer comes to mind: https://web.archive.org/web/20230610033639/https://old.reddit.com/r/HumanMicrobiome/comments/86btcd/gut_bacteria_determine_speed_of_tumor_growth_in/

And at what point is colon dysbiosis ruled out before diagnosing someone with SIBO? Never, from what I've seen. I don't even think such a thing is currently possible.

I see SIBO as, like other forms of dysbiosis, the lacking of certain microbes to keep in check the populations of other microbes. I think that often those missing microbes are likely phages [1], since phages are the natural "antibiotic" that keeps bacterial populations in check. So SIBO is not just "bacteria from the colon getting to where they're not supposed to be in the small intestine", but rather a lack of population-control-microbes. And depending on what your symptoms are (including the foods you can and can't tolerate), that should give some insight on which particular microbes are "out of control" with your particular form of dysbiosis (that varies drastically from person to person). Though as of yet that is undiagnosable due to current testing/sequencing limitations.

My email to Mark Pimentel, a leading researcher of SIBO: https://archive.fo/J3qw0#selection-1991.8-1995.0

Mar 2023, article critical about the SIBO hypothesis, and discussion about Pimentel's connections & funding with the company that makes Rifaximin: https://archive.ph/jdTnI#selection-3993.10-3993.11

Discussion on Dr Ruscio's 2019 SIBO review: https://archive.vn/46lZN#selection-2657.10-2657.11

Motility:

Some people argue that SIBO is caused by impaired motility, specifically the Migrating Motor Complex (MMC). But the gut microbiome regulates motility.

Review, Mar 2019: Obesity, Motility, Diet, and Intestinal Microbiota—Connecting the Dots https://link.springer.com/article/10.1007%2Fs11894-019-0680-y

Review, Jul 2022: Role of gut microbiota-derived signals in the regulation of gastrointestinal motility https://www.frontiersin.org/articles/10.3389/fmed.2022.961703/full

Neuronal programming by microbiota enables environmental regulation of intestinal motility (2019): https://www.biorxiv.org/content/10.1101/579250v1.full

Researchers find probiotics may increase intestinal motility in mouse model (April 2019): https://medicalxpress.com/news/2019-04-probiotics-intestinal-motility-mouse.html - Interactions Between Commensal Bacteria and Enteric Neurons, via FPR1 Induction of ROS, Increase Gastrointestinal Motility in Mice http://dx.doi.org/10.1053/j.gastro.2019.03.045

Microvesicles from Lactobacillus reuteri (DSM-17938) completely reproduce modulation of gut motility by bacteria in mice (Jan 2020) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225481

Microbiome-encoded bile acid metabolism modulates colonic transit times (May 2021, mice) https://www.cell.com/iscience/fulltext/S2589-0042(21)00476-4

Therapeutic effect of fecal microbiota transplantation on chronic unpredictable mild stress-induced depression (Jul 2022) https://www.frontiersin.org/articles/10.3389/fcimb.2022.900652/full "FMT improved symptoms of depression and colonic motility in rats exposed to CUMS"

The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time. (2012): https://doi.org/10.1111/j.1365-2982.2011.01819.x

Effects of Serotonin and Slow-release 5-HTP on Gastrointestinal Motility in a Mouse Model of Depression (May 2019): https://www.gastrojournal.org/article/S0016-5085(19)36715-0/fulltext

SIBO Treatment:

In regards to treatment of it, Rifaximin/Xifaxan is the "go to" antibiotic since it acts primarily in the small intestine. Anything (the large intestine) downstream will still be impacted by changes upstream though. There are also widespread claims that Rifaximin is harmless because it doesn't get absorbed. This claim makes no sense given that the concern is the damage to the gut microbiome. If anything, if it was absorbed it would do less damage to the gut microbiome.

19 patient trial showed Rifaximin not effective for SIBO (2014): https://doi.org/10.1186/s12941-014-0049-x - Discussion: https://archive.fo/k5MRy

2017 systematic review with meta‐analysis for rifaximin for SIBO https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299503/ "In the subset of studies (n= 10) allowing the analysis, improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7%. However, the quality of the available studies is generally poor."

The published literature on Rifaximin is very flawed: https://pubpeer.com/publications/3B347D455DF15FE1E693ADE3665543

Rifaximin is not harmless: https://archive.fo/qgWWS

More people significantly harmed by Rifaximin: [1][2][3][4][5][6].

More discussion of Rifaximin/Xifaxan/abx effectiveness & safety in comments: https://archive.fo/uDTvA

Mark Pimentel's 2003 study of 111 IBS patients showed 35% improvement for those who took neomycin, and 11% improvement for placebo. That's pretty abysmal, especially considering the severe long-term detriments from antibiotics.

FMT (Fecal Microbiota Transplants) for SIBO:

Current data shows that not only does top-down (capsules) FMT not cause SIBO, but it can treat it: https://humanmicrobiome.info/fmt#sibo

Restoring the gut microbiome should always be the first approach. Continually killing things off with antimicrobials will not restore eubiosis.

Summary:

The standard tests for it are inaccurate/useless.
The symptoms are non-specific so nothing can be said based on symptoms. So you can neither diagnose it off symptoms NOR testing.
You can induce "SIBO" via rectal FMT, and top-down FMT from adequate donors not only does not induce SIBO, but can treat it. So the notion that it's a matter of "microbes usually in the colon getting into the small intestine where they shouldn't be" is completely false.
The idea that there shouldn't be microbes in the small intestine is wrong. And any form of dysbiosis is an overgrowth of the wrong type of microbes.
Treatment outcomes are quite variable, and the standard antibiotic can have significant, long-term harms for some people.
Attempting to restore an ecosystem by continually killing off more species is an extremely flawed approach.

In my opinion, SIBO should have never made it to the clinical setting. It should still be confined to the research setting. I think that moving any portion of "IBS" or "general gut dysbiosis" diagnoses to "SIBO" is extremely premature and inaccurate.