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Review
. 2024 Feb 21;16(5):590.
doi: 10.3390/nu16050590.

Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives

Ahmed Noor Eddin  1 , Mohammed Alfuwais  1 , Reena Noor Eddin  1 , Khaled Alkattan  1 , Ahmed Yaqinuddin  1
Affiliations
Review

Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives

Ahmed Noor Eddin et al. Nutrients. .

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options are limited. However, recent evidence implicates gut dysbiosis and gut-brain axis (GBA) dysfunction in ALS pathogenesis. Alterations to the composition and diversity of microbial communities within the gut flora have been consistently observed in ALS patients. These changes are often correlated with disease progression and patient outcome, suggesting that GBA modulation may have therapeutic potential. Indeed, targeting the gut microbiota has been shown to be neuroprotective in several animal models, alleviating motor symptoms and mitigating disease progression. However, the translation of these findings to human patients is challenging due to the complexity of ALS pathology and the varying diversity of gut microbiota. This review comprehensively summarizes the current literature on ALS-related gut dysbiosis, focusing on the implications of GBA dysfunction. It delineates three main mechanisms by which dysbiosis contributes to ALS pathology: compromised intestinal barrier integrity, metabolic dysfunction, and immune dysregulation. It also examines preclinical evidence on the therapeutic potential of gut-microbiota-modulating agents (categorized as prebiotics, probiotics, and postbiotics) in ALS.

Keywords: amyotrophic lateral sclerosis; dysbiosis; gut modulation; gut-brain axis; microbiota; neurodegeneration; probiotics; therapeutics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Gut Dysbiosis and Pathology in Amyotrophic Lateral Sclerosis. Alterations to the gut microbiota can contribute to ALS pathology via three pivotal mechanisms: compromised gut barrier integrity, metabolic dysfunction, and immune dysregulation. Reduced expression of tight junctions along the intestinal epithelium allows for microbial invasion and subsequent inflammation. These microbes may also translocate into the blood, triggering a systemic immune response (e.g., endotoxemia, proinflammatory cytokine production, and peripheral monocyte activation). If prolonged, systemic inflammation can damage the blood–brain barrier (BBB) and result in the overactivation of microglia and astrocytes further aggravating neuroinflammation. The loss of immunomodulatory and neuroprotective metabolites such as butyrate, a short-chain fatty acid (SCFA), promotes motor neuron degeneration by increased oxidative stress and mitochondrial dysfunction. The interplay between gut and brain health highlights the therapeutic potential of gut–brain axis (GBA) modulation in ALS. Restoring a healthy microbial balance may not only alleviate patient symptoms by modulating these mechanisms but also prolong survival by mitigating disease progression. The figure was created using Biorender.com.
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