While SIBO (Small Intestinal Bacterial Overgrowth) is most associated with digestive symptoms - due to it being one of the main causes of IBS (Irritable Bowel Syndrome) - one of the most commonly reported symptoms is fatigue. In this post, I outline the various factors linking SIBO to fatigue so that you can feel more confident about the benefits that comprehensive SIBO treatment will have on many aspects of your health. Please know that large intestine dysbiosis can also create similar symptoms to SIBO, so the information in this article is relevant to that scenario too.
- Nutrient Deficiencies
- Sleep disturbances
- The stress of the condition itself
- Histamine producing bacteria, fatigue and brain fog
- The connection between gut dysbiosis and chronic fatigue syndrome
- The role of butyrate
- Hydrogen sulfide gas
- What you can do if you suspect you have fatigue connected to your gut health
The links between SIBO and fatigue are both direct and indirect. Some of them are due to direct physiological mechanisms and others are because SIBO and fatigue often have shared underlying causes. Some of the information comes from studies conducted on patients with Chronic Fatigue Syndrome (CFS), although many people with SIBO-related fatigue do not have CFS as such.
We should first identify what fatigue is. Fatigue can be both mental and physical. Cognitive fatigue often means having a specific time limit on cognitive (mental processing) exertion before an individual loses the ability to think clearly. “Brain fog” is another form of mental fatigue often reported in SIBO, which can be present regardless of how much an individual has exerted themselves cognitively. Brain fog feels just like a fog, the brain is slow and has a difficult time taking in information and then acting on it. Physical fatigue might feel like your body is moving slowly or with more effort. It can also feel like the need to lie down more often than normal or muscle fatigue, not always after exercise.
Below you will find clear explanations of the various links between SIBO and fatigue. My goal in writing this article is to empower you if you are struggling with fatigue so that you know there are plenty of options for treatment - obviously, it’s really important to work with someone who can accurately identify relevant factors.
Nutrient deficiencies are common in SIBO because our small intestine is where our nutrients are absorbed. An overgrowth of bacteria interferes with nutrient absorption because the bacteria actually consume nutrients such as B12 and iron - these two are crucial nutrients for adequate energy levels. So, the bacteria are consuming nutrients that are supposed to be for us.
A risk factor for SIBO is low stomach acid, which may or may not be due to use of PPI medication, hypothyroidism or low zinc for example. Low stomach acid itself can also cause these same nutrient deficiencies - so, this really drills home the point that getting to the bottom of why you have SIBO is so important. Low levels of B12 and/or iron are either due to the SIBO itself or an underlying low level of stomach acid (unless an individual just isn’t eating enough of the right foods).
In a study on fructose malabsorption (FM) - which is a proxy marker for SIBO according to Jason Hawrelak, PhD - levels of plasma folic acid (folate) are reduced. Similarly, in another study looking at zinc, the prevalence of zinc deficiency was much higher in the group with FM compared to those without. The mechanisms behind the effect of FM on nutrient absorption are currently not known.
In addition to iron and B12, SIBO often interferes with the absorption of fats - and fat soluble vitamins - due to its negative effect on bile function. Fats are essential to energy production, not only due to the supply of calories, but also because fats are used in energy production when they are burned.
Poor sleep makes most people feel fatigued. Sleep disturbances in SIBO come about for two main reasons: many bacteria typically found in SIBO are potent producers of histamine and bacteria found in SIBO interfere with the function of tryptophan.
Histamine is found in foods, is released by particular bacterial species and is also made by our body as part of normal functioning. Although it’s an essential molecule, the levels become too high in some individuals due to bacterial overgrowth, poor functioning of the DAO enzyme in the gut and impaired methylation. Histamine is a stimulating neurotransmitter, so levels that are too high and unable to be metabolised correctly can contribute to sleep disturbances along with anxiety.
In research conducted on people with fructose malabsorption, plasma levels of tryptophan are decreased. Tryptophan is an amino acid found in protein foods. Its role in the body is to convert to serotonin and then melatonin with the help of co-factors such as B6. Melatonin is essential for quality sleep, so a low level of available melatonin will negatively affect sleep and therefore energy levels.
A low carb diet, which many SIBO diets are by default, can also interfere with tryptophan uptake - this is another reason that a SIBO diet should only be temporary. There are many anecdotal stories of people whose sleep was negatively affected by lowering their carbohydrate intake, only for it to improve again when they were re-introduced to the diet. I don’t recommend just taking a tryptophan supplement instead, because a low carb diet may also negatively impact thyroid function - another common factor in fatigue states. Most of the evidence for that is currently anecdotal because not many research studies have been conducted on this specific topic. Still, it pays to be sensible and avoid removing entire macronutrients wherever possible. We know that gluconeogenesis - the production of glucose from protein that occurs during ketosis - relies heavily on cortisol production. Extended periods of high cortisol often lead to fatigue in the long run. Many diets - such as the ketogenic or very low carb diet - have a honeymoon period that could even last a few years before an individual’s health is significantly impacted negatively. And, finally, low carb diets are low in fermentable fibre, so they can impair the body’s ability to produce short chain fatty acids including butyrate - an energy source for the gut lining and also a source of calories for the individual. So, low levels of short chain fatty acids may contribute to fatigue in that regard.
And - finally - SIBO is strongly associated with restless legs syndrome (RLS), a sensorimotor disorder where an individual has a strong urge to move their limbs during periods of rest or inactivity. The condition occurs predominantly in the evening or overnight, so it has a strong negative effect on sleep quality. The mechanism is believed to be a deficiency of iron in the brain - as mentioned previously in this article, iron is a common nutrient deficiency in SIBO, caused by the bacteria consuming it, leaving the individual deficient.
The stress of the condition itself
Chronic stress and fatigue go together like a hand in glove. Chronic stress depletes our reserves and leads to ongoing fatigue if it’s not addressed. Dealing with SIBO is a form of stress - not just due to the frustrating symptoms - but also because of the psychological effects of trying to treat a chronic condition.
The good news is that there are so many interventions that can help here, from herbal medicines to specific nutrients. A full nutritional workup should be done for anyone with SIBO to check on the status of various nutrients.
Extended periods of high cortisol can also result in brain fog, partly because cortisol causes excessive excitation of brain cells that can kill them and cortisol can also reduce the rate at which new brain cells are made. Another possibility is that the brain fog someone is experiencing is actually dissociation, which is a common symptom in anxiety states. We know that anxiety and IBS often occur together.
Histamine producing bacteria, fatigue and brain fog
We’ve already covered the effect of histamine on sleep function above, but histamine can also contribute to fatigue and the feeling of brain fog. It’s suggested by mast cell expert Theo Theoharides that a high level of brain histamine turns on a negative feedback loop, such that the mast cells produce less histamine and histaminergic neurons slow down their activity, eventually leading to “brain fog”.
Mast Cell Activation Syndrome and Histamine Intolerance often co-occur with SIBO and IBS because there is a significant number of mast cells found in the gut. Theoharides proposes that bacteria-derived histamine can trigger additional release of histamine in the brain.
Hypothyroidism and Hashimoto's Thyroiditis are underlying risk factors for SIBO due to effects on stomach acid production and gut motility. Hypothyroidism also presents with ongoing fatigue as one of the main symptoms. So, in this case, it’s not the SIBO per se causing the fatigue, but the overall clinical context for that individual.
The connection between gut dysbiosis and chronic fatigue syndrome
SIBO is now known to be a form of dysbiosis and not just a simple overgrowth of bacteria. The REIMAGINE studies are working to elucidate the makeup of the small intestine microbiome and have so far found that people with SIBO have a much larger proportion of Proteobacteria (37%) compared to non-SIBO controls (11%). Many of the bacterial species found in the Proteobacteria phylum are known to be pro-inflammatory, partly due to the lipopolysaccharide (LPS or endotoxin) found in their cell walls. The abundance of Proteobacteria is also associated with a reduction in the diversity of species in the microbiome - this is also considered a key signature of dysbiosis.
So, it can be said that SIBO will likely cause similar issues to large intestine dysbiosis when it comes to chronic fatigue syndrome. Read my article all about how gut dysbiosis is currently understood and defined.
Numerous studies have been conducted looking at proxy markers of gut dysbiosis in order to determine if there is a link between dysbiosis and chronic fatigue syndrome. CFS is not a psychiatric condition, but it does share some similarities with various psychiatric conditions, in that what is known as “sickness behaviour” can be found in almost all of them. Sickness behaviour refers to the inability to feel pleasure with normal activities (anhedonia) and lack of motivation. It goes without saying that CFS involves a lot more than these characteristics - it often presents with poor immunity, muscle weakness and post-exertional malaise for example.
What the research suggests is that CFS may require a chronic proinflammatory state characterised and caused by increased intestinal permeability (“leaky gut”) and endotoxemia, which involves the translocation of bacterial antigens into the bloodstream. We know from animal models that endotoxemia presents as flu-like symptoms, inability to feel pleasure with normal activities (anhedonia) and lack of motivation. Two studies - here and here - found that increased circulating levels of proxy markers of gut dysbiosis (antibodies against endotoxins) were significantly associated with more severe symptoms of CFS.
Small Intestinal Fungal Overgrowth (SIFO) often co-occurs with SIBO and many of the symptoms are the same. Unfortunately, there is no direct test for SIFO, although elevated yeast markers on a Great Plains urinary organic acids test or on a stool test may be indicative, keeping in mind that the stool sample isn’t necessarily a representation of the small intestine microbiome. Yeasts produce a byproduct called acetaldehyde - also a metabolic product of alcohol - and this can cause brain fog.
The role of butyrate
Butyrate is a short chain fatty acid - a beneficial byproduct of fermentation made by gut bacteria. We know that short chain fatty acids - including butyrate - provide 5–15% of the total caloric requirements of humans, so it’s possible that a low level of butyrate may affect energy if there’s a caloric deficit.
Low butyrate is also one of the key markers of gut dysbiosis, it’s often present at low levels in conjunction with elevated Proteobacteria. That combination, as mentioned above, can lead to a chronic inflammatory state. Butyrate is a powerful anti-inflammatory substance, with both local effects and systemic effects.
Butyrate also helps to produce BDNF - Brain Derived Neurotrophic Factor - via intermediate production of a substance called FGF21 which is able to cross the blood brain barrier. BDNF encourages the growth of new neurons and also plays a role in muscle repair and regeneration.
In research looking at both CFS and fibromyalgia, the role of BDNF and whether it’s a positive or negative are both unclear. BDNF is also produced by the microglia in the brain as part of neuroinflammation - these are the immune cells of the brain, believed to be a factor in CFS. In three studies, the measured levels of BDNF varied between those with CFS and those without (control subjects) - in one study the levels were low, in another they were normal and in another they were elevated. Having said all that, it's unclear to what extent gut-bacteria-derived butyrate controls BDNF levels in the brain compared to the microglia, because most short chain fatty acids are either utilised in the gut or the liver, rather than being distributed systemically. As with many molecules, there is likely a "goldilocks" amount - not too much and not too little - that is best for optimal health.
Butyrate is also believed to be essential for adequate mitochondrial function - both in the gut and around the body - especially the brain, but also in skeletal muscle. It has been proposed as a neuroprotective substance and can help to produce ATP - the primary carrier of energy in cells. So it’s reasonable to suggest that a low butyrate state will affect fatigue via brain function and muscle activity due to effects on mitochondrial function.
Hydrogen sulfide gas
Hydrogen sulfide gas (H2S) plays an essential role in physiology but, as with many other substances, the right amount is needed. Too little will impair various processes and too much may also cause negative effects. H2S is produced by our own body but also many species of gut bacteria, some of which produce large amounts. The current research about the microbiome suggests that high levels of Proteobacteria - many species in this phyla produce H2S and also endotoxin (lipopolysaccharide) - is a common signature of dysbiosis. We also know from the REIMAGINE study that the small intestine microbiome in those with SIBO has a high level of Proteobacteria, and H2S SIBO is the third main type of SIBO.
The H2S gas in high amounts is toxic to the mitochondria - not only locally in the gut - but also systemically. Our mitochondria are energy producers within our cells. Dysregulation of H2S may play a role in fatigue since the gas can affect adenosine triphosphate (ATP) production from oxidative phosphorylation.
Over the last 12 years, there has been quite an emphasis on the role of H2S in CFS, with both laypeople and specialist doctors placing great emphasis on it. More recently, Dr. Greg Nigh ND has spoken about the role of H2S SIBO and he believes this type of SIBO (and excess H2S in general) is an adaptive response to a problem in the body accessing usable sulfur. I have covered this theory in more detail in this article about H2S SIBO.
What you can do if you suspect you have fatigue connected to your gut health
I always recommend working with a healthcare professional to determine where your fatigue is coming from, because it may be due to SIBO and related factors, hypothyroidism or nutrient deficiencies. I am trained in SIBO treatment and am well versed in the various causes of fatigue. Fatigue responds really well when the factors contributing to it are accurately diagnosed.
Find out how you can work with me to start feeling better.