Probiotics Prevent SIBO in Proton Pump Inhibitor Users

Proton pump inhibitor (PPI) medications are one of most frequently utilised classes of medicines. Primarily used to treat gastro-oesophageal reflux disease (GORD), gastritis and peptic ulcer disease, use of these medications has risen sharply over the past two decades. In fact, utilisation has increased by over 1300% over this time! Commonly used PPIs include omeprazole (Losec), lansoprazole (Zoton), esomeprazole (Nexium), pantoprazole (Somac) and rabeprazole (Pariet). Nexium alone accounts for over 19 million prescriptions in the US annually. In Australia, during 2013-14 there were over 19 million prescriptions written for PPIs – quite impressive for a nation of only 24 million people!

The capacity of PPIs to increase risk of Small Intestinal Bacterial Overgrowth (SIBO) had been debated (at least in some circles) until a meta-analysis published in 2013 showed conclusively that PPI use increased the odds of developing SIBO. Pooled data showed over a 7.5-fold increased risk of SIBO development in PPI users.

Given the substantial SIBO-risk associated with their use and the massive frequency of utilisation, it is not surprising that SIBO diagnosis and awareness has increased dramatically over the past decade. This is even more worrying in light of data suggesting that up to 70% of patients taking PPIs are doing so inappropriately!

So, is there anyway to decrease the risk of SIBO development in those patients taking PPIs? It turns out that the right probiotic preparation is indeed capable of reducing the risk of SIBO development.

In a very recent randomised, controlled trial, 128 patients with GORD were allocated to receive either a probiotic supplement or placebo alongside their PPI over a 12-week period. The probiotic group received the strain Lactobacillus reuteri DSM 17938 at a dose of 5 drops per day of an oil preparation (containing a total of 1 x 10^8 CFU/day). SIBO assessment was done (via the Glucose Breath Test) at baseline and again after 12 weeks PPI treatment (esomeprazole). No patients tested positive for SIBO at baseline. Amazingly, SIBO developed in over 56% of patients taking the PPI in the placebo group in just 12 weeks! On the other hand, SIBO only developed in 6% of subjects in the PPI + probiotic group (group difference P<0.001). Additionally, significantly more children in the placebo group developed new gastrointestinal symptoms compared to those in the probiotic group (P=0.026).

This study clearly showed that the co-ingestion of this specific probiotic strain was capable of preventing SIBO from developing in patients taking PPIs. Is this something we could expect from just any probiotic preparation? The research suggests not, with a previous study finding an alternative probiotic preparation comprised of two probiotic strains (Lactobacillus rhamnosus R0011 & L. acidophilus R0052) prescribed at a higher dose (2.0 x 10^9 CFU/day combined) was unable to prevent SIBO development in PPI users. So, at this point, we’d have to conclude that this is an action potentially unique to the L. reuteri DSM 17938 strain.

So, how does this strain work to prevent SIBO from developing? It may have to do with the ability of this strain to produce an anti-microbial compound called reuterin. Reuterin has demonstrated broad action against a range of microorganisms that are commonly found to be overgrown in patients with SIBO – Escherichia, Proteus, Pseudomonas, Staphylococcus, Streptococcus, Enterococcus and Bacteroides spp..

I’ve always argued that probiotics can play pivotal roles in the treatment of SIBO and now we have excellent evidence showing that the right probiotic can prevent its development too.

Jason Hawrelak
Chief Research Officer
Probiotic Advisor

Selected references:
Axelsson LT, Chung TC, Dobrogosz WJ, et al. (1989). Production of a broad spectrum antimicrobial substance by Lactobacillus reuteri. Microbial Ecology in Health and Disease 2(2):131-136.

Belei O, Olariu L, Dobrescu A, et al. (2018). Is it useful to administer probiotics together with proton pump inhibitors in children with gastroesophageal reflux? J Neurogastroenterol Motil 24(1):51-57. PMID: 29291607

Forgacs, I., & Loganayagam, A. (2008). Overprescribing proton pump inhibitors. BMJ, 336(7634), 2-3. doi: 10.1136/bmj.39406.449456.BE
Hollingsworth S, Duncan EL, Martin JH. (2010). Marked increase in proton pump inhibitors use in Australia. Pharmacoepidemoil Drug Saf 19(10):1019-1024.

Lo, W. K. and W. W. Chan (2013). “Proton Pump Inhibitor Use and the Risk of Small Intestinal Bacterial Overgrowth: A Meta-analysis.” Clinical Gastroenterology and Hepatology 11(5): 483-490.

Just what is a “leaky vagina”? And why we should care about it…

I’ve just returned from the MINDD Conference in Sydney where I was invited to present lectures to both health professionals, and the general public, on the functions and importance of the vaginal microbiota.

One of the concepts I brought up at the conference was the idea of a “leaky” vagina. Many of us are very aware of the consequences of a leaky gut or leaky blood-brain barrier. But few of us have considered the concept of a leaky vagina – or what impact this may have on a woman’s health.

What are the known risks? Well increased risk of genital herpes infection, as well as human papilloma virus (HPV) infection and its sequelae cervical cancer, for two. Given this, I wonder why optimisation of the vaginal ecosystem is not a core component of a women’s preventative healthcare strategy.

The vaginal microbiota is the “poor cousin” of the GIT microbiota – it has only just begun to get the research interest it deserves. Research conducted over the last 5 years has clearly shown that an optimal vaginal ecosystem (i.e., an ecosystem dominated by D-lactate-producing lactobacilli species) is associated with enhanced fertility, better birth outcomes, and reduced risk of sexually transmitted diseases and recurrent urinary tract infections, as well as reduced HPV infection rates (a necessary precursor to cervical cancer).

So how many women have an optimal vaginal microbiota? Sadly, research suggests not that many – with some research finding only about 40% of women having ecosystems dominated by D-lactic acid-producing species (Lactobacillus crispatus, L. gasseri, and L. jensenii).

One final consideration is that we are only now finding out some of the ramifications of having a “leaky” vaginal wall. Other consequences will surely be teased out in the upcoming years. We know a dysbiotic vaginal microbiota containing large numbers of Gram-negative bacteria and a deficiency of lactic acid-producing lactobacilli leads to a leaky vagina. This is due to the vital role of lactic acid, specifically D-lactic acid, in the growth and repair of vaginal epithelial cells.

Undoubtedly, the combination of dysbiosis and increased permeability to bacterial by-products like endotoxins (from Gram-negative bacteria) will add to a woman’s inflammatory load. This may directly impact reproductory organs and contribute to diseases like endometriosis (see the paper on the bacterial contamination hypothesis below), but also have systemic sequalae. With inflammation now seen to be a key driver of most, if not all, chronic Western diseases, it is about time to highlight this issue.  We know that GIT dysbiosis can contribute to systemic inflammatory load, but we now need to consider that vaginal dysbiosis can do likewise in women.

We, as clinicians, need to start assessing the health of this ecosystem in all of our female patients. A simple pH test strip (with accurate gradations between pH 3.5-5.5) is all that is needed for an initial screen for vaginal dysbiosis – with a pH >4.5 a clear indication of a dysbiotic ecosystem in pre-menopausal women.

Jason Hawrelak
Chief Research Officer
Probiotic Advisor

Select References:

Borgdorff H, Tsivtsivadze E, Verhelst R, Marzorati M, Jurriaans S, Ndayisaba GF, et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J. 2014;8(9):1781-93

Hyman, R. W., Herndon, C. N., Jiang, H., Palm, C., Fukushima, M., Bernstein, D., . . . Giudice, L. C.. The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer. J Assist Reprod Genet. 2012; 29(2), 105-115.

Khan KN, Fujishita A, Hiraki K, et al. Bacterial contamination hypothesis: a new concept in endometriosis. Reprod Med Biol 2018;17(2):125-33. doi: 10.1002/rmb2.12083

Kirjavainen, P. V., Pautler, S., Baroja, M. L., Anukam, K., Crowley, K., Carter, K. & Reid, G. 2009. Abnormal Immunological Profile and Vaginal Microbiota in Women Prone to Urinary Tract Infections. Clin. Vaccine Immunol. 2009; 16, 29-36.

Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR, Kyrgiou M. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next? Microbiome. 2016;4(1):58

Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol. 2015;6:81.

Younes, J. A., Lievens, E., Hummelen, R., van der Westen, R., Reid, G., & Petrova, M. I. Women and Their Microbes: The Unexpected Friendship. Trends in Microbiology. 2017;26(1), 16-32.