Sunday, March 12, 2017

Battling Small Intestinal Bacterial Overgrowth (SIBO) With Probiotics | Some Bugs as Effective (50%) as Antibiotics

Battling bacteria w/ more bacteria. Sounds odd, but works like a charm.
Those who haven't made the mistake not to "like" the SuppVersity on Facebook may already have seen it in the news: SIBO, i.e. the overgrowth of bacteria in the small intestine, may be linked to heart disease. The link, according to a study by Ponziani, et al. (2017), who found a significantly elevated arterial stiffness in SIBO patients, could be a combination of inflammation and a lack of vitamin K.

More common and obvious complaints of SIBO patients include gastrointestinal discomforts and malabsorption. Eventually, the on-going bacterial overgrowth can yet also have systemic inflammatory effects and the translocation of bacteria into the gut stream displays a persistent risk factor for sepsis (Quigley 2006).
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Unfortunately, the not exactly abundant currently available research indicates, as Zhong et al. write in their latest paper in the Journal of Clinical Gastroenterology that "antibiotics alone may be inadequate for SIBO decontamination" (Zhang 2017). This is bad news because, as previously hinted at, ...
Figure 1: Bacterial flora along the gastrointestinal tract; relative concentrations of bacteria at various points in the adult human intestine. Note these concentrations apply only to species that can and have been cultured (Quigley 2006).
"[...] the delicate balance between host and environment is central to intestinal homeostasis. The intestinal epithelium is exposed on a daily basis to the bacterial antigens of the commensal microflora that in turn induce a state of controlled inflammation. This physiologic response to bacterial antigens is not harmful to the host and generates both the induction of immune tolerance and the secretion of immunoglobulin A (IgA). [...] In disease states, a proinflammatory response to these same luminal antigens leads to the development of such disorders as celiac sprue and inflammatory bowel disease" (Quigley 2017) 
Next to the well-known localized bowel-related consequences, SIBO can also trigger weight loss as well as vitamin and mineral deficiencies due to defective nutrient uptake. In this context the following nutrients are particularly worth mentioning (Dukowicz 2007):
  • fat-soluble vitamins A, D, E, K, as well as vitamin B12, and iron
  • dietary protein (high risk of hypoalbuminemia)
Folate, on the other hand, may be produced/absorbed in excess (that's because of an increased synthesis of folate by small bowel bacteria | Camilo 1996).
Proton pump inhibitors do not cause SIBO, but they sign. increase your risk of developing it: Even though Ratuapli et al. write in their 2012 study that "[i]n [their] large, adequately powered equivalence study, PPI use was not found to be significantly associated with the presence of SIBO as determined by the GHBT", studies using more accurate measures of SIBO than the glucose hydrogen breath test (e.g. duodenal or jejunal aspirate culture) suggest that it clearly predisposes to the development of SIBO - with PPI users being 7-8-fold more likely to develop SIBO than non-users (Lo 2013) - to which extent this may be thwarted by primary diseases, the type of PPI (older studies show much higher SIBO rates) and the administration frequency is unfortunately not addressed in either Lo's meta-analysis or the individual studies.
In observational studies, SIBO has even been linked to Parkison's disease (Gabrielli 2011; Fasano 2013), cirrhosis (=liver disease | Gupta 2010), fibromyalgia (Pimentel 2001) and other diseases and syndromes. For all of them, however, the links are putative and a causal involvement of SIBO has yet to be demonstrated.
Table 1: If you want to know if you suffer from SIBO, don't do the lactulose breath test. It's intolerably inaccurate. Plus: As Lo et al. point out, all diagnostic breath tests for SIBO may simpler to administer, less invasive, and less costly than duodenal/jejunal aspirate culture, they are yet also comparatively less sensitive and specific (Lo 2013).
I guess that you will still be interested in the usefulness of probiotics in SIBO therapy - in spite of the correlative nature of the previously mentioned links between SIBO and life-threatening diseases, right? Well, this is what Zhong et al. did and found: Using all the usual databases, they identified studies that (1) assessed the efficacy of probiotics for preventing or treating SIBO; (2) enrolled  >10 patients; and (3) displayed the prevention outcomes or treatment outcomes. To exclude studies that do not meet these criteria data, two authors independently screened the initially 393 records. Eventually, Zhang et al. ended up with 18 studies that were pooled into the meta-analysis. Here's what they found:
  • Do probiotics prevent the occurrence of SIBO? Six studies investigated the occurrence of SIBO in patients with probiotics use. The pooled analysis of all studies suggested that patients using probiotics exhibited a slight predisposition toward a decreased incidence of SIBO when compared with those not using probiotics, but without statistical significance (RR=0.63; 95% CI, 0.29-1.36; P=0.24) (Fig. 2). Also, high heterogeneity was presented (I2=84.4%, P<0.05).
    Figure 2: FIGURE 2. Forest plot showing the incidence of SIBO for probiotic users compared with the nonprobiotic users. CI indicates confidence interval; RR, relative risk; SIBO, small intestinal bacterial overgrowth (Zhang 2017).
    However, the evaluation solely including the RCTs displayed an insignificant result (RR=0.54; 95% CI, 0.19-1.52; P=0.24), without a substantial change in the heterogeneity (I2=83.7%, P<0.05).
  • Do probiotics help with SIBO eradication? The pooled decontamination rate from studies using either probiotics alone and studies using probiotics + antibiotics was 62.8% (51.5% to 72.8%), with high heterogeneity (I2=71.1%, P<0.05).
    Figure 3:  Pooled SIBO decontamination rate, grouped by probiotics alone or probiotics plus antibiotics. CI indicates confidence interval; SIBO, small intestinal bacterial overgrowth (Zhang 2017)
    The pooled rate of successful treatment was 53.2% (40.1% to 65.9%) for probiotics alone and 85.8% (69.9% to 94.0%) for probiotics plus antibiotics. Individual studies testing both confirm the superiority of antibiotics vs. probiotics as a stand-alone treatment with the former yielding beneficial effects in 38% vs. 18% (Saad 2014).

    A different image emerges when we compare antibiotics, alone, vs. antibiotics + probiotic trials. Here, Zhang's results suggested that patients with SIBO using probiotics have a significantly higher SIBO decontamination rate compared with the nonprobiotic users (RR=1.61; 95% CI, 1.19-2.17; P<0.05), and a lower level of heterogeneity (I2=25.7%, P=0.25).
If you review the results you will have to admit that it remains questionable whether antibiotics are dispensable. What appears to be certain, however, is that their combination with probiotics will yield the greatest chance of successfully battling SIBO.

Furthermore, their chronic use may, as the data in Figure 2 indicates, protect you from developing SIBO - in particular if you belong to one of the SIBO risk groups because of structural/anatomic features such as small intestine diverticula, small intestine strictures, surgically created blind loops, resection of ileocecal valve, etc., motility disorders such as gastroparesis, small bowel dysmotility, celiac disease, etc., IBS or metabolic disorders such as diabetes, or hypochlorhydria, organ system dysfunction, including, cirrhosis, renal failure, pancreatitis, etc., or medications such as antibiotics and drugs that suppress the gastric acid production.
You may remember that VSL#3 has been in the SuppVersity news before... for it's ability to reduce the fat over the course of 4 weeks of overfeeding twenty young men (caloric surplus 1000 kcal/day on a high fat (55%) diet) by impressive >50%. For all these studies, you got to keep potential conflicts of interest in mind | more.
So, if probiotics work, which and how much do I take? I know that many of you don't care about anything of what I've written about. The only thing you want is exact advice which products you should buy. Ok, let's see. The strains that were used are: (1) Bacillus clausii at a dosage of 2 bn CFU twice a day for one month in Scarpellini et al. (2006 | 57% success rate), and the same dosage thrice daily in Gabrielli, Maurizio, et al. (2009 | success rate of 48%); (2) L. casei strain Shirota in Barrett et al. (2008), in form of one bottle of Yakult® (6.5x10^9 + 1 g lactose per dose), consumed daily for 6 weeks this yielded an impressive success rate of 64%; (3) VSL#3 a proprietary mix of Bifidobacteria, Lactobacilli and Streptococcus thermophilus at a dosage of 110bn CFU with improvements of SIBO in 58% of the subjects w/ cirrhosis; (4) Duolac Gold probiotic containing Bifidobacteria, Lactobacilli and Streptococcus thermophilus at a dosage of 5 bn viable cells in a lyophilized powder form with a relatively low improvement rate of 24% - likewise in patients with liver cirrhosis.

In the short run Soifer et al. saw benefits with one of the often-seen mixes of Lactobacillus casei (3.3 x 10^7 UFC), Lactobacillus plantarum (3.3 x 10^7 UFC), Streptococcus faecalis (3.3 x 10^7 UFC) and Bifidobacterium brevis (1.0 x 10^6 UFC). The product (Bioflora) was yet administered for only 7 days and the only outcome measure were subjective intestinal complaints. Similarly semi-useless measured were used by Ockeloen, et al. (2012) who administered a single capsule with 1 × 10^9 Bifidobacterium and Lactobacillus per day,

As you may guess, it is - without head-to-head comparisons - difficult to tell which of the products would be your best choice. Personally, though, I would gravitate to (1)-(3) from the list above as they've been used in the longer run and with inaccurate, but at least direct breath tests for SIBO instead of simple improvements in gastrointestinal complaints. If that's not going to work you can still resort to Rifaximin at a dosage of >800mg/d (here, more helps more | Lauritano 2005) and restore a healthier microbiome w/ post-antibiotic probiotic therapy | Comment or ask questions!
  • Barrett, Jacqueline S., et al. "Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome." World J Gastroenterol 14.32 (2008): 5020-5024.
  • Camilo, Ermalinda, et al. "Folate synthesized by bacteria in the human upper small intestine is assimilated by the host." Gastroenterology 110.4 (1996): 991-998.
  • Dukowicz, Andrew C., Brian E. Lacy, and Gary M. Levine. "Small intestinal bacterial overgrowth: a comprehensive review." Gastroenterol Hepatol (NY) 3.2 (2007): 112-22.
  • Fasano, Alfonso, et al. "The role of small intestinal bacterial overgrowth in Parkinson's disease." Movement Disorders 28.9 (2013): 1241-1249.
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  • Gabrielli, Maurizio, et al. "Prevalence of small intestinal bacterial overgrowth in Parkinson's disease." Movement Disorders 26.5 (2011): 889-892.
  • Gupta, Ankur, et al. "Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy." Journal of hepatology 53.5 (2010): 849-855.
  • Kwak, Dong Shin, et al. "Short-term probiotic therapy alleviates small intestinal bacterial overgrowth, but does not improve intestinal permeability in chronic liver disease." European journal of gastroenterology & hepatology 26.12 (2014): 1353-1359.
  • Lauritano, Ernesto Cristiano, et al. "Rifaximin dose‐finding study for the treatment of small intestinal bacterial overgrowth." Alimentary pharmacology & therapeutics 22.1 (2005): 31-35.
  • Lo, Wai–Kit, and Walter W. Chan. "Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis." Clinical Gastroenterology and Hepatology 11.5 (2013): 483-490.
  • Lunia, Manish Kumar, et al. "Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial." Clinical Gastroenterology and Hepatology 12.6 (2014): 1003-1008.
  • Ockeloen, L. E., and J. M. Deckers-Kocken. "Short-and long-term effects of a lactose-restricted diet and probiotics in children with chronic abdominal pain: a retrospective study." Complementary therapies in clinical practice 18.2 (2012): 81-84.
  • Pimentel, Mark, et al. "Small intestinal bacterial overgrowth: a possible association with fibromyalgia." Journal of Musculoskeletal Pain 9.3 (2001): 105-113.
  • Ponziani, et al. "Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms." World J Gastroenterol. 2017 Feb 21;23(7):1241-1249. doi: 10.3748/wjg.v23.i7.1241.
  • Quigley, Eamonn MM, and Rodrigo Quera. "Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics." Gastroenterology 130.2 (2006): S78-S90.
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  • Soifer, L. O., et al. "Comparative clinical efficacy of a probiotic vs. an antibiotic in the treatment of patients with intestinal bacterial overgrowth and chronic abdominal functional distension: a pilot study." Acta gastroenterologica Latinoamericana 40.4 (2010): 323-327.
  • Zhang, et al. "Probiotics for Preventing and Treating Small Intestinal Bacterial Overgrowth: A Meta-Analysis and Systematic Review of Current Evidence." Journal of Clinical Gastroenterology: April 2017 - Volume 51 - Issue 4 - p 300–311 doi: 10.1097/MCG.0000000000000814.