The Role of the Microbiota–Gut–Brain Axis and Antibiotics in ALS and Neurodegenerative Diseases
Open accessAbstract
The human gut hosts a wide and diverse ecosystem of microorganisms termed the microbiota, which line the walls of the digestive tract and colon where they co-metabolize digestible and indigestible food to contribute a plethora of biochemical compounds with diverse biological functions. The influence gut microbes have on neurological processes is largely yet unexplored. However, recent data regarding the so-called leaky gut, leaky brain syndrome suggests a potential link between the gut microbiota, inflammation and host co-metabolism that may affect neuropathology both locally and distally from sites where microorganisms are found. The focus of this manuscript is to draw connection between the microbiota–gut–brain (MGB) axis, antibiotics and the use of “BUGS AS DRUGS” for neurodegenerative diseases, their treatment, diagnoses and management and to compare the effect of current and past pharmaceuticals and antibiotics for alternative mechanisms of action for brain and neuronal disorders, such as Alzheimer disease (AD), Amyotrophic Lateral Sclerosis (ALS), mood disorders, schizophrenia, autism spectrum disorders and others. It is a paradigm shift to suggest these diseases can be largely affected by unknown aspects of the microbiota. Therefore, a future exists for applying microbial, chemobiotic and chemotherapeutic approaches to enhance translational and personalized medical outcomes. Microbial modifying applications, such as CRISPR technology and recombinant DNA technology, among others, echo a theme in shifting paradigms, which involve the gut microbiota (GM) and mycobiota and will lead to potential gut-driven treatments for refractory neurologic diseases.
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Neurodegenerative alterations are caused by a complex combination of genetic, environmental, and transgenic interactions, which are more closely linked than previously believed.
“Neurodegenerative alterations are caused by a complex combination of genetic, environmental, and transgenic interactions, which are more closely linked than previously believed (84).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [84]
Beta-lactams (cephalosporin antibiotics) have been shown to be effective in the treatment and alleviation of ND symptoms and in the treatment of experimentally induced neurological disorders such as PD, AD, ALS, traumatic brain injury, epilepsy, cerebral ischemia, and neuropathy.
“In particular, beta-lactams (cephalosporin antibiotics) have been shown to be effective in the treatment and alleviation of ND symptoms and in the treatment of experimentally induced neurological disorders such as PD, AD, ALS, traumatic brain injury (TBI), epilepsy, cerebral ischemia, and neuropathy (84, 117, 118).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [84]
CFT has been reported to have neuroprotective and anti-inflammatory effects, to protect neurons from oxidative stress and ionizing radiation, and to act as a free radical scavenger.
“CFT has been reported to have neuroprotective and anti-inflammatory effects, to protect neurons from oxidative stress and ionizing radiation, and to act as a free radical scavenger (84).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [84]
There is bidirectional communication between the gut and the brain.
“Increasing evidence suggests there is bidirectional communication between the gut and the brain [6–8].”
From Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota (2021) · cites this paper as [8]
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Self-citationComplete heart block due to lyme carditis.
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Importance of Glutamate Dehydrogenase (GDH) in Clostridium difficile Colonization In Vivo
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Recent findings within the microbiota–gut–brain–endocrine metabolic interactome
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The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases
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Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders
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Is gut microbiota of patients with ALS different from that of healthy individuals?
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Special Issue: Microbiota–Gut–Brain Axis
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Chattopadhyay, M., Laskar, A., Rahaman, S. S., & Chanda, A. (2025) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815324549125010010
Gut Microbiota and Amyotrophic Lateral Sclerosis
Vahabzadeh, G., & Golab, F. (2025) · The Neuroscience Journal of Shefaye Khatam · doi:10.61882/shefa.14.1.117
Additional file 1 of Medication use and risk of amyotrophic lateral sclerosis—a systematic review
Cui, C., Sun, J., McKay, K. A., Ingre, C., & Fang, F. (2022) · Figshare · doi:10.6084/m9.figshare.20438328
Inhibition of Aβ(40) peptide aggregation by Milk-derived Amyloid-like Protein Aggregates (MAPA)
Malik, S., De, I., Yadav, A. S., Poonia, V., Gaur, K., Goyal, P., Singh, M. P., & Yadav, J. K. (2026) · Biological Chemistry · doi:10.1515/hsz-2025-0208
Therapeutic Interventions: Modulating the Microbiome to Combat Neurodegeneration
Anandan, A., Unais, A. M., Prabhu, A. V., Saju, M. K., Sonaimuthu, K., Murugesan, H., Danielraj, F., Marimuthu, D., Shibu, M. A., & Viswanadha, V. P. (2026) · Springer eBooks · doi:10.1007/978-981-95-7494-0_8
- Authors
- Obrenovich, M., Jaworski, H., Tadimalla, T., Mistry, A., Sykes, L., Perry, G., & Bonomo, R.
- Affiliations
- Cleveland State University (US)
- Louis Stokes Cleveland VA Medical Center (US)
- MetroHealth (US)
- The University of Texas at San Antonio (US)
- Corresponding author
- Obrenovich, Mark
- Venue
- Microorganisms
- Publisher
- MDPI AG
- Published
- 2020-05-23
- Volume
- 8
- Issue
- 5
- Pages
- 784
- ISSN
- 2076-2607 (ISSN-L)
- PMC
- PMC7285349
- OpenAlex
- W3027244878
- Cited by
- 62
- References
- 128
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 7 · 2023: 14 · 2022: 11 · 2021: 13 · 2020: 3
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Microorganisms (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- gut microbiota, microbiota-gut-brain axis, antibiotics, amyotrophic lateral sclerosis, neurodegenerative diseases, Alzheimer's disease, mood disorders, schizophrenia, autism spectrum disorder, leaky gut, neuroinflammation, fungal communities, CRISPR, personalized medicine
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