The gut microbiome and neuroinflammation in amyotrophic lateral sclerosis? Emerging clinical evidence

Abstract Background Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. Main body The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. Conclusion Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.

Download Full-text

Motor-evoked potentials in amyotrophic lateral sclerosis: potential implications in detecting subclinical UMN involvement in lower motor neuron phenotype

Journal of Neurology ◽

10.1007/s00415-020-10073-5 ◽

2020 ◽

Vol 267 (12) ◽

pp. 3689-3695

Author(s):

Stefano Zoccolella ◽

Antonella Mastronardi ◽

Antonio Scarafino ◽

Giovanni Iliceto ◽

Eustachio D’Errico ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Evoked Potentials ◽

Motor Neuron ◽

Clinical Evidence ◽

Motor Evoked Potentials ◽

Clinical Signs ◽

Lower Motor Neuron ◽

Diagnostic Certainty ◽

Reliable Marker ◽

Lateral Sclerosis

Abstract Background In amyotrophic lateral sclerosis (ALS), the involvement of lower motor neuron is well defined by electromyography, whereas a reliable marker of upper motor neuron (UMN) damage still lacks. Aim of the study was to estimate the role of transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) as marker of subclinical UMN involvement. Methods Clinical evidence of UMN damage was prospectively compared to MEPs in 176 ALS patients diagnosed between 2011 and 2014, and classified according to existing diagnostic criteria. Finally, we evaluated the appearance of clinical UMN signs and the level of diagnostic certainty in ALS after 1 year of follow-up. Results At presentation, abnormal MEPs were found in 80% of patients with clinical evidence of UMN damage and in 72% of patients without clinical involvement of UMN. Among these latter, 61% showed appearance of UMN clinical signs after 1 year. Approximately 70% of patients with clinical lower motor neuron (LMN) phenotype showed MEP abnormalities, while they were considered not classifiable ALS according to Airlie house or Awaji criteria. Furthermore, abnormal MEPs in absence of clinical UMN signs at baseline were found in 80% of spinal ALS that after 1-year developed UMN signs at limbs, compared to 50% of bulbar ALS. Conclusions TMS is a reliable marker of subclinical UMN damage particularly among LMN phenotype and ensure an early ALS diagnosis in ~ 70% of such cases.

Download Full-text

The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients

Scientific Reports ◽

10.1038/s41598-020-69845-8 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Qianqian Zeng ◽

Jie Shen ◽

Kangzhi Chen ◽

Jinxia Zhou ◽

Qiao Liao ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Gut Microbiome ◽

Lateral Sclerosis

Download Full-text

Gut microbiome differences between amyotrophic lateral sclerosis patients and spouse controls

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration ◽

10.1080/21678421.2021.1904994 ◽

2021 ◽

pp. 1-9

Author(s):

Vicki S. Hertzberg ◽

Harinder Singh ◽

Christina N. Fournier ◽

Ahmed Moustafa ◽

Meraida Polak ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Gut Microbiome ◽

Lateral Sclerosis

Download Full-text

Adipose-derived stem cell conditioned medium for the treatment of amyotrophic lateral sclerosis: pre-clinical evidence and potential for clinical application

Neural Regeneration Research ◽

10.4103/1673-5374.253514 ◽

2019 ◽

Vol 14 (9) ◽

pp. 1522 ◽

Cited By ~ 1

Author(s):

ChandlerL Walker

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Stem Cell ◽

Conditioned Medium ◽

Clinical Application ◽

Clinical Evidence ◽

Adipose Derived Stem Cell ◽

Cell Conditioned Medium ◽

Lateral Sclerosis

Download Full-text

Effects of Biofeedback Training on Esophageal Peristalsis in Amyotrophic Lateral Sclerosis Patients with Dysphagia

Journal of Clinical Medicine ◽

10.3390/jcm9072314 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2314

Author(s):

Jerzy Tomik ◽

Klaudia Sowula ◽

Piotr Ceranowicz ◽

Mateusz Dworak ◽

Kamila Stolcman

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Clinical Evidence ◽

Specific Pattern ◽

The Body ◽

Biofeedback Training ◽

Esophageal Peristalsis ◽

Swallowing Function ◽

Promising Tool ◽

Als Patients ◽

Lateral Sclerosis

Esophageal manometry (EM) could serve as an objective method for the detection of esophageal peristalsis in patients with amyotrophic lateral sclerosis (ALS). In this group of patients, biofeedback training (BT) using the EM procedure is a promising method for the rehabilitation of swallowing function. A total of 20 ALS patients with clinical evidence of dysphagia and who met WFN criteria were recruited for this study. The standard transnasal EM with solid-state transducers was performed, and swallows with water and saliva were initiated in all subjects and repeated at 30-s intervals. The median upper esophageal contractile amplitude, duration, and velocity results during the wet and dry swallows were evaluated and compared in both the ALS and the control groups. In ALS patients, in contrast to the control, significant abnormalities in all EM parameters were recorded, which implies a specific pattern of esophageal peristalsis. Twelve months after BT, the body mass index (BMI) of ALS patients who underwent BT (ALSBT) was compared to the BMI of those who did not (ALS1)—compared to the ALS1 group, ALSBT patients showed a slightly smaller drop in BMI value. We presume that BT using EM can be a promising tool for the improvement of the swallowing mechanism in ALS patients.

Download Full-text

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

Journal of Speech Language and Hearing Research ◽

10.1044/2019_jslhr-19-00178 ◽

2020 ◽

Vol 63 (1) ◽

pp. 59-73 ◽

Cited By ~ 3

Author(s):

Panying Rong

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Acoustic Analysis ◽

Speaking Rate ◽

Disease Stage ◽

Healthy Controls ◽

Tongue Movement ◽

Major Barrier ◽

Syllable Repetition ◽

Oral Diadochokinesis ◽

Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

Download Full-text