The Gut Microbiome and Amyotrophic Lateral Sclerosis (ALS)

In recent years, the gut microbiome, a complex ecosystem of microorganisms residing in the gastrointestinal tract, has garnered increasing attention for its influence on human health, often in surprising ways. Emerging research suggests a potential link between the gut microbiome and amyotrophic lateral sclerosis (ALS), a debilitating neurodegenerative disease characterized by the progressive loss of motor neurons. In this article, we delve into the intricate relationship between the gut microbiome and ALS, exploring how imbalances in the microbial community may contribute to the pathogenesis of this devastating condition.
Frederika Malichová

Frederika Malichová

Dementia Researcher at the University Of Cambridge.

An image showing the gut microbiome and motorneurons.

Gut Health And ALS: Connecting The Dots

The Gut Microbiome

To understand the connection between gut health and ALS, we must first understand the gut microbiome. The gut microbiome refers to the collection of microorganisms, including bacteria, viruses, fungi, and other microbes, that reside in the gastrointestinal tract. The exact composition of the gut microbiome is influenced by our diet, but also genetics or environmental exposures.

The microorganisms that reside in our gastrointestinal tract play a significant role in digestion, nutrient absorption or the synthesis of certain vitamins and metabolites. Interestingly, it turns out that the role of the gut microbiome in the human body is much more complex and extends far beyond the digestive system [1,2,3].

In recent years, the gut microbiome has become the subject of intense scientific research, because of its potential role in various diseases. In our previous blog, we wrote about the gut-brain connection, and how the gut microbiome may impact mental health. In this blog post, we will examine the intriguing connection between the gut microbiome and ALS, highlighting yet another aspect of the microbiome's influence on human health.

What is Amyotrophic Lateral Sclerosis?

Amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, is a neurodegenerative disease that affects the nerve cells in the brain and spinal cord. It leads to progressive degeneration and loss of motor neurons, which are responsible for controlling voluntary muscle movement. The symptoms of ALS can vary from person to person, but commonly include [4,5]:

  1. Muscle weakness: ALS typically begins with muscle weakness, often in the hands, arms, legs, or feet. This weakness may cause difficulty with tasks such as gripping objects, walking, or climbing stairs.
  2. Muscle atrophy: As the disease progresses, the muscles may start to shrink or waste away (atrophy), leading to a loss of muscle mass.
  3. Spasticity: Some individuals with ALS may experience muscle stiffness and spasms, known as spasticity. This can make movement and coordination more difficult.
  4. Muscle cramps and twitching: Many people with ALS experience muscle cramps and involuntary muscle twitching, known as fasciculations.
  5. Difficulty speaking and swallowing: ALS can affect the muscles involved in speech and swallowing, leading to slurred speech, difficulty articulating words, and problems with swallowing.
  6. Breathing difficulties: As the disease progresses, the muscles involved in breathing may weaken, leading to shortness of breath, difficulty breathing, and eventually respiratory failure. It's important to note that ALS is a progressive disease, meaning that symptoms worsen over time.

How Does the Gut Microbiome Influence ALS?

At first glance, the connection between the gut microbiome and ALS may seem shocking. Researchers began investigating the idea that gut health may affect ALS after they observed that many ALS patients suffer from constipation, which worsens as the disease progresses.

Studies conducted on both animals and humans have indicated that individuals with ALS exhibit alterations in their gut microbiota compared to healthy counterparts. For example, a large human study [6] compared ALS patients with age and sex-matched healthy controls and identified differences between these two groups in various microbial genera. They determined that as the disease progresses, a decrease in the number of present bacteria in the gut is observed. This suggests a link between the microbiota composition and the progression of the disease.

Other studies found very concrete links between levels of particular bacteria in the gut and ALS symptoms. A study conducted on mice discovered that mice suffering from ALS had decreased levels of a bacteria called Butyrivibrio fibrisolvens in their gut microbiome. Naturally, the researchers wanted to find out whether supplementation of this bacteria in ALS patients could influence the symptoms of the disease. Thus, the same research group performed another study on mice and discovered that the supplementation improved intestinal barrier function, delayed weight loss and even death in mice with ALS in comparison to healthy controls [7,8].

This connection between Butyrivibrio fibrisolvens and ALS is not random. It is believed that a contributing factor to the progression of ALS and the degeneration of motor neurons is neuroinflammation, which, as the name suggests, is inflammation that occurs in the central nervous system [9]. Importantly, the bacteria Butyrivibrio fibrisolvens is thought to be responsible for modulating neuroinflammation, by producing butyrate, a short-chain fatty acid [7]. This is one possible explanation of how ALS and gut health are linked.

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There is more evidence linking gut microbiome and ALS. In separate studies, it has been proposed that the repeated use of antibiotics negatively impacts the gut microbiota[10,11].

Consequently, researchers decided to investigate the effect of antibiotics on ALS. One study conducted experiments on mice, and showed that repeated use of antibiotics was associated with increased neuronal loss and the development of a more severe motor phenotype of ALS [12].

Interestingly, a study by Sun et al analyzed whole-population data of Sweden, and likewise reported that repeated use of antibiotics can increase the risk of developing ALS [13].

These studies further support the claim that gut microbiota health is indeed linked to ALS symptoms manifestation.

Explaining the Possible Mechanisms of Influence: How the Gut Microbiota Impacts ALS

Numerous possible mechanisms have been proposed which might explain the link between the gut and microbiota. The dysregulation of the gut microbiota in ALS may contribute to disease pathogenesis (loss of neurons) through mechanisms involving impaired gastrointestinal integrity, immune system dysregulation, altered metabolism, and the production of neurotoxic or neuroprotective metabolites [6,7,8,14,15,16]. Concretely, we have the following possible mechanisms of influence:

  1. Metabolite Production: The gut microbiota generates metabolites that can traverse the bloodstream and influence the central nervous system. These metabolites may exert neuroprotective or neurotoxic effects, potentially shaping the progression of ALS.
  2. Immune System Modulation: Interactions between the gut microbiota and the immune system can lead to dysregulation in ALS. This immune imbalance contributes to inflammation and neuronal damage, hallmark features of the disease.
  3. Intestinal Barrier Integrity: Disruptions in the gut microbiota can compromise the integrity of the intestinal barrier, resulting in increased permeability and the leakage of harmful substances into the bloodstream. This phenomenon, known as "leaky gut" may contribute to systemic inflammation and impact the course of ALS.

While the exact mechanisms linking the gut microbiome to ALS are still being investigated, the abovementioned findings suggest the role of gut microbiota may play in the pathogenesis of ALS.

Can We Prevent or Alleviate ALS By Having a Healthy Gut?

As we have discussed, there is evidence linking the disease progression and gut microbiota. But what can we do with the information? Can we alter the symptoms of ALS by bettering our gut microbiome?

As we mentioned previously, animal models indicate that supplementing with specific bacteria can ameliorate ALS symptoms. Another study conducted by Zhang et. al. further supports this. The researchers wanted to see whether the restoration of microbiome and intestinal homeostasis can modify the onset and progression of ALS. The findings of their study were shocking - they identified the natural bacterial product butyrate as effective in extending the lifespan of ALS mice by 38 days [17].

Other bacteria, such as Akkermansia muciniphila, Parabacteroides distasonis or Ruminococcus torques have also been identified as having an impact on ALS [17]. Importantly, some bacteria can make the symptoms worse. Try asking MediSearch about the possible impact of these bacteria on ALS:


Aside from bacteria supplementations, other interventions have been suggested. Pharmacological vitamin supplementation and an individualized ketogenic dietmay be effective in reducing the rate of motor neuron degeneration in both ALS animal models and ALS patients [18]. These studies suggested Vitamin B12, Vitamin E and Vitamin C to be significant in the reduction of ALS risk and Vitamin B9, B2, B1 and B6 to be moderately significant in the ALS risk reduction.

However, it is important to note that the evidence is not as clear-cut as it may seem from the previous sections. Di Gioia et al. performed a longitudinal study on the gut microbiota and ALS and determined that even though probiotic supplementation improved the overall composition and diversity of the gut microbiota, this study did not find any amelioration of ALS symptoms [6].

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Conclusion

We can see that there is a communal effort to bridge the gap from animal research to human relevance. Although these microbial interventions might present a tantalizing avenue for potential future ALS therapies, the evidence is still conflicting and a consensus has to be made [6,7,8,15,19]. However, if there indeed is a link between the gut microbiome and ALS, these findings, as highlighted by Guo et al. (2023), not only could provide crucial mechanistic insights into ALS but also hold promise in identifying robust disease biomarkers.

Disclaimer

This article does not offer health advice. Always consult a medical professional regarding your condition.

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Frederika Malichová

Frederika Malichová

Frederika is a postgraduate researcher at the University of Cambridge, where she investigates new biomarkers for Frontotemporal Dementia and other tauopathies. Her research has been published at prestigious conferences such as the Alzheimer’s Association International Conference 2023. She obtained her BSc in Biomedical Sciences from UCL, where she worked closely with the UK Dementia Research Institute.