Gut Health: Imbalanced Gut Flora Equals Leaky Gut

Intestinal permeability also known as leaky gut can stem from many different causes. Any ongoing insult to the gut can lead to increased permeability. Read on to learn how an imbalanced gut flora can lead to leaky gut and what to do about it.

A Primer On Leaky Gut

Keeping it simple intestinal permeability, also known as leaky gut, occurs when the tight junctions in the small intestine become more permeable. This allows molecules (think poorly digested foods, microbes like bacteria and yeast cells) cross the intestinal wall that wouldn’t normally pass.

There are countless insults to the gut wall that can increase permeability.

This state of increased permeability has been linked to different disease states including, among others, irritable bowel syndrome and inflammatory bowel disease.

Leaky gut has even been proposed as being a required for the development of autoimmune diseases. That is a pretty big statement. Currently it is a working theory. We’ll see if the science can back it up as we move forward.

Bacterial Imbalance Causing Leaky Gut

Understanding the root cause of your intestinal permeability is important when we look towards solutions in fixing it. Today we are covering bacterial imbalances and opportunistic bacterial overgrowths in the large intestine, known as dysbiosis, causing leaky gut.  

A paper was published recently on the subject of intestinal permeability and some possible solutions. It was a cracker!

Here’s the link if you want to dive a bit deeper – The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation

One interesting point they bring up (one that herbalists and naturopaths have known for some time) is the idea of an imbalanced gut flora, aka dysbiosis, leaking to leaky gut.

The idea revolves around inflammation, an overgrowth of less friendly bacteria and the resulting impact on the gut barrier.

Inflammation – Imbalanced Gut Flora and Intestinal Permeability

First let’s talk about the impact that certain bacteria can have, creating an inflamed environment. 

Bacteria are classified as either gram positive or gram negative. This is a very important distinction to make as gram negative bacteria contain a very immunogenic substance in their cell wall known as lipopolysaccharide, or endotoxin.

Immunogenic – relating to or producing an immune response

Many opportunistic and at times outright pathogenic bacteria are gram negative. These include different Citrobacter species (2) Campylobacter species, one of the top causes of gastroenteritis (3), Klebsiella species. See here for information on Klebsiella pneumoniae infections. Helicobacter pylori needs no introductions here. While it can and does cause a range of gut issues in many people that carry this bacteria there has been talk of some benefits that it provides. These include speculations on it’s possible protective effect against inflammatory bowel disease (4).

For anyone steeped in microbiology you can see a trend emerging. Each and every one of these different bacteria belong to the phylum Proteobacteria. Each and everyone, apart from Campylobacter belongs to the family Enterobacteriaceae.

They are all gram-negative bacteria.

Now here is where it gets interesting.

According to the review paper, in a healthy gut ecosystem Proteobacteria is present in very small numbers. When this balance is disrupted and the different members of the Proteobacteria phylum are allowed to grow, their endotoxin rich cell walls trigger an inflammatory cascade leading to intestinal permeability or leaky gut.

Side Note On Bacterial Strain Specificity  

Just a little mention on the beauty of diversity and not painting every bacterial strain with the same brush. Although many strains of Escherichia coli are proinflammatory and can cause issues such as urinary tract infections there is one specific beneficial strain known as Escherichia coli Nissle 1917.

This particular strain, marketed as mutaflor, is used as a beneficial probiotic and there is some evidence out there showing its application in maintaining remission in ulcerative colitis.

Not only does it play interference with invading less-than friendly E. coli strains it also has been shown to have an anti-inflammatory effect and to improve leaky gut (5).

More on that in a future article.

What Can Be Done In This Situation

Here we can see a situation that isn’t normally discussed. In the past there has been an over emphasis on one particular bug. I am as guilty as the next one of thinking in this reductionist manner.

While it is true that one particular pathogenic strain of bacteria can cause serious gut damage, here I’m thinking of Clostridium difficile which can be particularly nasty (6), the concept of the gut as an ecosystem might be a better way to approach the situation.

The constant insult on the population of indigenous bacteria by broad spectrum antibiotics and a low fibre diet (among other things) leads to an imbalanced gut. An imbalanced gut leads to overgrowths of opportunistic, proinflammatory microbes, leading to increased intestinal permeability (leaky gut).

Probiotics From The Future

Here we circle back to the review and cover some important new(ish) bacteria on the block.

First off Bifidobacteria is mentioned. While this isn’t particularly new to the research it is worth noting some of the benefits that this genus of bacteria provides for our guts.

Different Bifidobacteria species can help by

• Protecting the gut barrier
• Modulate the immune system
• Cross feed other beneficial bacteria found in the gut

Next onto some less known bacteria starting with Akkermansia muciniphila. This particular beneficial bacteria helps in a number of ways

• It cross feeds other beneficial bacteria in the gut
• Uses up the toxic hydrogen sulfide made by certain sulfate-reducing bacteria in the gut thus limiting exposure
• Production of antimicrobial peptides thus limiting opportunistic bacterial growth
• Increasing mucin production which layers over the gut wall
• Protection against atherosclerosis by limiting the inflammation caused by endotoxins passing from the gut into the blood (a term called translocation)

Interestingly this is a gram negative bacteria demonstrating that some gram negative bacteria can be beneficial.

Onto Faecalibacterium prausnitzii. This one could be familiar to you from a past article.

It’s a superstar microbe.

• It feeds the cells in the large intestine known as colonocytes
• Helps to maintain immune balance
• Strengthens and heals the gut barrier
• It is a major fermenter, producing butyrate a potent anti-inflammatory compound which may have protective effects against colorectal cancer.

Roseburia intestinalis

• Another short chain fatty acid producer this particular bacteria produces butyrate in abundance
• Anti-inflammatory effects
• Upregulation of T regulatory cells which modulate the immune system toning down an overactive response which is characterised by autoimmunity.

Eubacterium hallii

This is a new one to me.

• It is another major butyrate producer
• Has an anti-inflammatory effect
• Cross feeds and is cross fed by other beneficial bacteria  

Bacteroides fragilis

Finally Bacteroides fragilis benefits the gut in a number of novel ways .

• It secretes a specific immunomodulating substance known as polysaccharide A which then activates T regulatory cells which helps to modulate or tone down an overactive immune system.
• Improves and reinforces the gut barrier
• Is anti-inflammatory

Image taken from: The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation

Where To Find These Incredible Probiotic Bacteria

Here’s the rub.

None of these bacterial species are available (except for the Bifidobacteria strains).

Currently the probiotics that are available do not stick around in the gut for very long after supplementation stops. As these next generation bacteria appear to have the ability to colonise the human gut and take up residence their lack of availability is a shame.

But, and this is a big but. We can work with what we currently have. Here I am talking about prebiotic supplementation.

How To Support Your Native Gut Flora, Boost Beneficials And Reduce Likelihood Of Disease

That was a mouthful. But I don’t think there is a better way to put it.

Nurturing our resident gut ecosystem by feeding it prebiotics, suitable resistant starches, colonic foods and fibre is a great place to start. Maybe in the not too distant future we can access these super hero bugs as a probiotic capsule for now fermentable oligo, di, monosaccharides are helpful, specifically prebiotics that have been shown to selectively feed the beneficial bacteria.

Digging into the research is one thing. Actually experimenting and seeing how you feel is another. Different probiotics that I have tried and noticed a benefit from include

• Lactulose – particularly in cases of Blastocystis infections (and other protozoan infections too)
  
• Acacia gum – This is a very slow burning prebiotic, meaning that it doesn’t get consumed immediately by the first suitable bacteria. The take home point here is that it is available throughout the large intestine as a food source for selective beneficial bacteria.
• Partially hydrolysed guar gum – This is a very very interesting prebiotic. I can feel a dedicated article coming up on it shortly. There is research showing it improves constipation (Partially Hydrolyzed Guar Gum Accelerates Colonic Transit Time and Improves Symptoms in Adults with Chronic Constipation) boosts Bifidobacterium and Lactobacillus species while simultaneously decreasing fecal pH, ammonia and putrefaction products (Effects of Partially Hydrolyzed Guar Gum Intake on Human Intestinal Microflora and Its Metabolism) and improving IBS symptoms (Treatment Effects of Partially Hydrolyzed Guar Gum on Symptoms and Quality of Life of Patients with Irritable Bowel Syndrome. A Multicenter Randomized Open Trial). And we’re only just getting started!
• Inulin (or FOS) – This one I am liking slightly less so now that I have discovered and experimented with the others. Please don’t get me wrong I have nothing against inulin and much of the research points to it being a great immune booster. For me it more a feeling. I feel much better on the prebiotics listed above. They appear to be slower burning prebiotics (I know not the highest level of science there, but we can’t forget that how you feel is one of the most important guides in treatment)
• GOS – This is one that I have been reading about and am very interested in. Unfortunately you have to order it in from overseas and I just haven’t gotten around to it yet. I will provide an update when I do.

Treat The Gut Like An Ecosystem

In wrapping it all up we’ve talked about the gut as an ecosystem.

An impacted gut ecosystem, much like any other ecosystem, acts and reacts to the insult in profound ways. The growth of opportunistic bacteria, particularly from the phylum Proteobacteria, leads to a pro-inflammatory state. Driven by the lipopolysaccharide endotoxins the intestinal barrier is damaged, leading to leaky gut.

The immune system is sent into overdrive.

Opposing this process are some superhero bugs, including Bifidobacteria, Akkermansia muciniphila, Faecalibacterium prausnitzii, Roseburia intestinalis, Eubacterium hallii and Bacteroides fragilis. Many of these bacterium produce short chain fatty acids, reducing the pH and promoting and anti-inflammatory state in the gut. Some secrete antimicrobial peptides and others help to balance the immune system and promote T regulatory cells.

As these specific bacteria (apart from Bifidobacterium) are not available as probiotics it is important to care for the ones that are residing in you now. Prebiotics, increasing your dietary fibre and focusing on colonic foods will go a long way in bringing your gut back into balance and keeping it there.

Have you had any experiences with probiotics and prebiotics? Share your thoughts in the comments below.

 References and Resources

1. The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation
2. Citrobacter Infections in Humans: Experience at the Seattle Veterans Administration Medical Center and a Review of the Literature
3. EPIDEMIOLOGY OF CAMPYLOBACTER JEJUNIINFECTIONS
4. Helicobacter pylori: beneficial for most?
5. Role and mechanisms of action of escherichia coli nissle 1917 in the maintenance of remission in ulcerative colitis patients: an update
6. Clostridium difficile infection: a review of current and emerging therapies