Microbial Influences on Amyotrophic Lateral Sclerosis: The Gut–Brain Axis and Therapeutic Potential of Microbiota Modulation

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dc.contributor.authorAyala Jové, Ma. Victoria (Maria Victoria)
dc.contributor.authorFontdevila Olivé, Laia
dc.contributor.authorRico-Rios, Santiago
dc.contributor.authorPovedano, Mònica
dc.contributor.authorAndrés Benito, Pol
dc.contributor.authorTorres Cabestany, Pascual
dc.contributor.authorSerrano Casasola, José Carlos Enrique
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorPortero Otín, Manuel
dc.date.accessioned2025-07-17T06:55:36Z
dc.date.available2025-07-17T06:55:36Z
dc.date.issued2025
dc.description.abstractBackground/Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons. The gut microbiota, a community of microorganisms in the digestive tract, has recently been implicated in ALS pathogenesis through its influence on neuroinflammation and metabolic pathways. This review explores the potential role of digestive microbiota and its metabolites in ALS progression and investigates therapeutic approaches targeting gut microbiota. Methods: A comprehensive review of the current literature was conducted to assess the relationship between gut microbiota composition, microbial metabolites, and ALS progression in patients. We searched for published reports on microbiota composition, microbial metabolites, and ALS, emphasizing the complex interplay between dysbiosis, neuroinflammation, and systemic metabolism. Special emphasis was placed on studies exploring short-chain fatty acids (SCFAs), bacterial amyloids (curli-like factors), and neurotoxins such as β-methylamino-L-alanine (BMAA). The role of the liver–gut axis was evaluated as well. The potential changes in microbiota would sustain the rationale for therapeutic strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions. Results: ALS patients exhibit gut dysbiosis, characterized by reduced SCFA-producing bacteria and an increase in potentially pathogenic genera. Of note, different studies do not agree on common patterns of microbiota being linked to ALS, supporting the need for further, more extensive studies. Dysbiosis sometimes correlates with systemic inflammation and disrupted liver function, amplifying neuroinflammatory responses. Key microbial metabolites, including SCFAs, bacterial amyloids, and BMAA, may exacerbate motor neuron degeneration by promoting protein misfolding, oxidative stress, and neuroinflammation. Emerging therapeutic strategies, including probiotics and FMT, show potential in restoring microbial balance, although clinical data in ALS patients remain limited. Conclusions: The gut microbiota could modulate neuroinflammation and systemic metabolism in ALS. Microbiota-targeted therapies, such as probiotics and dietary interventions, represent promising avenues for mitigating disease progression. Further research is required to validate these interventions through large-scale, longitudinal studies and to develop personalized microbiota-based treatments tailored to individual ALS phenotypes.
dc.description.sponsorshipThis work is supported by grants from Instituto de Salud Carlos III (PI20/000155 and PI23/00176), Generalitat de Catalunya (2021 SGR 00990), Miquel Valls Foundation (Jack Van den Hoek donation), FUNDELA, and RedELA funds. This work was also supported by Ministerio de Ciencia, Innovación y Universidades, throughout the MIdAS network.
dc.identifier.doihttps://doi.org/10.3390/sclerosis3010008
dc.identifier.issn2813-3064
dc.identifier.urihttps://hdl.handle.net/10459.1/468364
dc.language.isoeng
dc.publisherMDPI
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.3390/sclerosis3010008
dc.relation.ispartofSclerosis, 2025, vol. 3, núm. 1, 8
dc.rightscc-by (c) Victòria Ayala et al., 2025
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectProbiotics
dc.subjectMotor neuron disease
dc.subjectDysbiosis
dc.subjectNeuroinflammation
dc.titleMicrobial Influences on Amyotrophic Lateral Sclerosis: The Gut–Brain Axis and Therapeutic Potential of Microbiota Modulation
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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