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).
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).
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.
References:

• 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.
• Gabrielli, Maurizio, et al. "Bacillus clausii as a treatment of small intestinal bacterial overgrowth." The American journal of gastroenterology 104.5 (2009): 1327.
• 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.
• Ratuapli, Shiva K., et al. "Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth." The American journal of gastroenterology 107.5 (2012): 730-735.
• Scarpellini, E., et al. "Bacillus clausii treatment of small intestinal bacterial overgrowth in patients with irritable bowel syndrome." Digestive and Liver Disease 38 (2006): S32.
• 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.