As of December 8, 2024 we found a new clinical trial on fecal transplants in patients with ALS. This trial showed no benefits on ALS progression. Thus we change our “Trials” grade from U to F. It is important to note that the sample size of this was very small and as a result the trial was probably underpowered. Also, the protocol used did not persistently change the gut microbiome in enrolled participants. We hope to see future trials with larger sample sizes and improved treatment regimens that will persistently change the gut micriobiome.
Since our last review we found a new report describing 2 patients with ALS whose clinical course improved in association with fecal transplants. This does not change our previous TOE Cases Grade of A. We hope to see the results of a trial of fecal transplants for ALS soon.
Since our last update, we found a new case report published in a peer reviewed journal (J Biomed Res. 2022 Jun 28:1-8. doi: 10.7555/JBR.36.20220088. Online ahead of print). This described a person with ALS who received a series of fecal transplants and then had their ALS progression improve. The authors nicely describe the limitations of associations like this, especially given the known variability in ALS progression in individuals over time. Although it has to be interpreted with caution, this published case warrants a change in our TOE “Cases” grade to A. We look forward to the results of an ongoing trial of this therapy in people with ALS (https://clinicaltrials.gov/ct2/show/NCT03766321?term=fecal&cond=ALS&draw=2&rank=1).
Since our initial review we found 3 new relevant preclinical studies (Amyotrophic Lateral Scler Frontotemporal Degen 2017;18:245–6; Nature 2019;572:474-480; Nature 2020;582:89-94). These suggest plausible mechanisms by which fecal transplants could slow ALS progression, including modulating neuroinflammation and neuroprotection. As a result, we change our TOE “Mechanisms” grade from D to B. These show that in 3 different ALS animal models, changing the gut microbiome favorably slows disease progression. As a result, we change our TOE “Pre-Clinical” grade from U to B. We found no new case reports, trials, or risks to warrant grade changes in those TOE categories.
These new studies warrant a change in our conclusion as well. Fecal transplants (and other ways to change the gut microbiome) now appear to be more promising. We are glad to see ongoing efforts to define “good” and “bad” microbiomes in patients with ALS, and trials to try and change microbiomes to slow, stop or reverse progression (NCT04499963, NCT03766321).
Key Information
There is rapidly expanding evidence implicating alterations in the fecal microbiome in wide-ranging human diseases, including potential contributions via a gut-brain signaling axis in neurodegenerative and neuroimmunologic disorders. Proposed mechanisms such as immune modulation and the production of neurotoxins by clostridia or other microbiota could bypass an intact blood-brain barrier. To date, there are no data directly implicating the fecal microbiome in ALS, nor published case reports of FMT being tried in PALS. Data in other neurodegenerative and neuroimmunologic disorders are largely circumstantial, comprising a handful of published case reports. Therefore, ALSUntangled does not recommend FMT as a treatment for ALS at this time. However, it is plausible that the fecal microbiome plays a role in some neurologic disorders, including ALS. Given the lack of effective therapies and the relatively low cost and low risk of FMT – if performed by experienced clinical centers we support further investigations in this developing field. A reasonable next step would be a detailed molecular analysis of gut bacteria in ALS patients; certainly, these are the types of studies being advocated by the NIH Human Microbiome Project. If alterations are detected in the gut microbiome of ALS patients, a following step would be properly controlled studies in animal models, such as ALS mice. These studies could employ the same germ-free, and/or probiotic treatment regimens published in mouse models of EAE, Alzheimer’s disease, and obesity.