SIBO : Digestive Enzymes and the Pancreas

Today we’re covering the link between the pancreas and SIBO, aka small intestinal bacterial overgrowth and the big question is ‘do all SIBO patients need strong digestive enzymes to fully recover?

There is a curious pattern in many SIBO patients having lab low elastase-1 on testing. 

Image showing low pancreatic elastase on stool testing

Elastase 1 is quite an accurate, low cost and non-invasive test showing how active your pancreas is on the digestive enzyme front. It isn’t thrown off by external enzyme supplementation too which is handy (1). 

A gastroenterologist would use this lab along with other diagnostic criteria to rule in or rule out a condition called exocrine pancreatic insufficiency or EPI. Anything below 200 micrograms of elastase 1 per gram of stool should be looked at carefully by a prescribing doctor (2).

‘Exocrine pancreatic insufficiency may initially present with non-specific symptoms, such as bloating, abdominal discomfort, steatorrhoea, diarrhoea, excess flatulence and weight loss’

Othman et al, 2018

These symptoms look a heck of a lot like SIBO and I’ve seen many SIBO positive patients with low elastase 1 who have improved dramatically on good strong digestive enzymes which is the mainstay of EPI treatment.  

Testing For Low Enzyme Production with SIBO

So the first step here is to determine whether you have SIBO or not.

Surprisingly testing for SIBO is more contentious than you might think. Below are my thoughts on SIBO testing after years of treating this condition.

Once you know you are SIBO positive or not the next step is to determine your root cause and treat both the bacterial overgrowth causing your symptoms (bloating, gas, distention, abdominal pain, food reactions, etc) and address the reason why – ie the root cause.

If you don’t address the root cause of SIBO then the chance of relapse is high.

Any functional stool test worth the cost of the lab will be testing for elastase-1.

The labs that I’ve reviewed in my clinical practice that do test for enzyme production from the pancreas include

  1. Complete Microbiome Mapping – Nutripath
  2. GI-MAP – Diagnostic Solutions
  3. GI-360 – Drs Data
  4. GI-Effects – Genova Diagnostics

Now you might be thinking that involvement of the pancreas and low enzyme production is uncommon and if you follow the literature you’ll see that the most common causes for EPI are very serious conditions like chronic pancreatitis (the most common), pancreatic tumours, cystic fibrosis and conditions like coeliac disease and inflammatory bowel disease (4).

Let me tell you here, I see lab low elastase 1 frequently (remember I can’t diagnose any conditions) so I’ll refer patients here back to their prescribing doctor to get worked up and rule out any of the significant diseases and underlying conditions of EPI. 

So far, and I’m not saying it doesn’t happen, not one of the patients that we’ve clocked this issue with has had a serious condition with their pancreas. And almost every one of these patients, bar two, have had SIBO! 

So far almost every patient I’ve seen with lab low enzyme production from the pancreas has had SIBO

Now that doesn’t mean that there isn’t an overlap with the common drivers of EPI and SIBO. In fact a systematic review looking at the frequency of SIBO in chronic pancreatitis saw that over ⅓ of patients with chronic pancreatitis had SIBO (5).

That’s a whopping number! 

As always we’re trying to find and treat the root cause we’ll need to determine whether SIBO causes the low enzyme output from the pancreas or does low enzyme production cause SIBO? Which way does it go?  

Low Pancreatic Enzymes cause SIBO

We have good evidence showing that poor enzyme production from the pancreas can cause small intestinal bacterial overgrowth and the biggest piece to support this is that proteolytic enzymes and the pancreatic fluid are both antibacterial (6, 7).

We have one study (true on dogs) showing that EPI led to small intestinal bacterial overgrowth and that when they were supplemented with pancreatic enzymes it reversed the SIBO (8). This is a huge insight into how impactful poor enzyme production from the pancreas can be on the microbiome balance in the small bowel.

SIBO causing low Pancreatic Enzymes production

On the other side of things there is the case to be made that SIBO can lead to EPI and the resulting symptoms and this poor enzyme production could then lead to a persistence of the bacterial overgrowth in small bowel. A bit of a vicious loop!

We know that the majority of EPI cases are from conditions that lead to damage to the actual pancreas organ but remember I see frequently EPI in the clinic and have never seen this common root cause of organ damage before. I still refer back each and every patient with lab low elastase 1 to their prescribing doctor to be thoroughly evaluated 

Something else must be going on. 

We see EPI as a result of some coeliac and inflammatory bowel disease cases due to ‘a loss of intestinal brush border proteins’ (9) which would equate to damage to the gut lining and intestinal hyper-permeability. 

Now we’re not quite there in the literature but I am comfortable saying that in most of my patients with SIBO and EPI there is evidence of gut damage and even leaky gut either as

  • high zonulin
  • a positive on the lactulose mannitol leaky gut testing

Here we can see a link between that damage and a lack of response from the pancreas leading to poor release of digestive enzymes, leading to less control of bacterial growth in the small bowel, leading to more gut damage and around we go! 

Now what to do about it? 

Approaches to SIBO Treatment With Digestive Enzymes

I would typically approach these two issues we’ve outlines above, SIBO and low enzyme production from the pancreas or EPI if you have that diagnosis head on and simultaneously

#1. Supplement with pancreatic enzymes  

Using strong animal based digestive enzymes like these ones

#2. Treat the bacterial overgrowth head on at the same time

Herbs, probiotics and prebiotics are the mainstay for SIBO treatment in the Byron Herbalist clinic.

#3. Heal and seal the leaky gut! 

Generally I’ll hang off and recommend gut healing support after we have worked through treating SIBO.

Now over to you. Do you have any experience with SIBO and enzyme supplementation? Leave me a comment below!

References and Resources

  1. Fecal Elastase-1 as a Test for Pancreatic Function: a Review
  2. Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test
  3. Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician
  4. Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis
  5. Systematic review and meta-analysis: Small intestinal bacterial overgrowth in chronic pancreatitis
  6. Small intestinal bacterial overgrowth syndrome
  7. Antibacterial Activity of the Pancreatic Fluid
  8. The fecal microbiome of dogs with exocrine pancreatic insufficiency
  9. Less common etiologies of exocrine pancreatic insufficiency
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  1. Middle aged, active, thin/athletic dad here. Very much appreciate the article and the references. I have dx of EPI (1st test Moderate, 2nd test was in Severe range). I’m on a (very) high dose of Creon. Before taking Creon, I took prescription dose PPI and it helped with better stool formation.
    Subsequently, I have been found to have mild SIBO. I’m about to start antibiotic for 2 weeks (rifaximin).
    Cause of EPI is undetermined. Celiac and all common culprits are not looking very applicable. Pancreas imagining and lots of bloodwork is all good. An abdominal MRI is forthcoming.

    Question: After completing Rifaximin, I want to make sure SIBO doesn’t return. What’s easiest way to maintain that? LowFODMAP or herbal supplements? If so, which one’s?


  2. I would like to know if I am one of those people! All I know is my mom had pancreatitis, so possibly that set me up for low pancreatic enzyme and is maybe the root cause of my SIBO. Boy, if there is a simple explanation to all this suffering and a path forward, I’m all for finding out!

    1. Some cases can be quite tricky! I’ve found focusing on pillars of digestive health are key, enzyme production from the pancreas, balanced microbiome in the large bowel and good quality gut motility too! From there I’ll layer more complex treatments on only if needed.
      Hope that helps!

  3. 34 and going through it. It’s scary bc the pancreas is no joke. I have EPI and SIbo out of nowhere. Can’t wrap my head around it. Many imaging and even an EUS to look at pancreas. Confusion is doctor mentioned Chronic pancreatitis but then back stepped and said “likely a normal pancreas” which is it???

  4. This is really helpful to see. I have EPI and SIBO, and an MCRP to the pancreas indicated no damage (thankfully!).

    I am encouraged to see that low elastase is a marker that is not as uncommon as it seems, and that there is a connection to SIBO, which I know I have. Digestive enzymes and probiotics seem to help me!

    1. Creon is a script based enzyme so I leave that to the prescribing doctors. The pancreatic enzymes available to the general public (pancreatin) are the same but not as strong.

  5. Such a good article. Keep up the good work. I’ve learned a lot from you when I was treating my SIBO. But when I relapsed I decided to go to my GP and my results showed mild elastase production. Ultrasound looked normal but I’m currently waiting for referral for further examination. It’s hard put my finger on what is causing the low enzyme as I live a very healthy lifestyle (no alcohol, just organic food & active lifestyle). So is it the SIBO connection. Interestingly I also have issues with bile but again I don’t know what’s causing what.

  6. I noticed by accident that after a xifaxin treatment for sibo When my probiotic ran out I switched to a new one that had digestive enzymes And there was an immediate decrease in phytoestrogen sensitivity. This was obvious because of the acne that’s associated with it was immediately decreased and should have been profound due to my accidental consumption of soy lecithin.
    I have been nutritionally deficient on the level of vitamins and minerals. It will be another month or so before I test my vitamins again. There seems to be a direct correlation with a decrease in pre-diabetic symptomology.
    I am not sure if I was tested for pancreatic issues. However, this will be brought up with my gastroenterologist as well as the endocrinologist.
    This happy accident has given me hope. It pays to be observant. In fact, it’s why I looked up information and found this article which gave a correlation.

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