Repeated antibiotic use carries heightened risk of subsequent amyotrophic lateral sclerosis

Individuals with repeated antibiotic use are at increased risk of developing amyotrophic lateral sclerosis (ALS), a recent study has found.

Researchers conducted a nested case–control study using data from several Swedish national registers. They identified 2,484 ALS patients as cases, each of whom were matched to five non-ALS controls randomly selected from the general Swedish population. Data on antibiotic prescriptions before ALS diagnosis was obtained from the Prescribed Drug Register for both cases and controls.

The mean age at diagnosis was 68.6 years for patients with ALS, and more than half (56.7 percent) of the entire population were men. Male ALS patients were generally younger than their female counterparts (mean, 67.9 vs 69.7 years; p=0.0002).

ALS patients overall were more likely to have had received antibiotics prescriptions compared with controls (65.1 percent vs 61.8 percent; p=0.0018). This higher rate could be traced as far back as 6–8 years before ALS diagnosis, with the rate difference peaking during the year before diagnosis.

In a conditional logistic regression model accounting for potential diagnostic delay in ALS by excluding all prescriptions within 1 year before diagnosis, any antibiotics use was associated with a higher risk of ALS compared with nonuse (1 prescription: odds ratio [OR], 1.06, 95 percent CI, 0.94–1.19; 2–3 prescriptions: OR, 1.13, 1.00–1.28; ≥4 prescriptions: OR, 1.18, 1.03–1.35; p-trend=0.0069).

Similar results were observed for antibiotics used for respiratory and urinary tract infections, as well as skin and soft tissue infections. With regard to antibiotic types, the relationship with subsequent ALS was strongest for >2 prescriptions of beta-lactamase sensitive penicillin (OR, 1.28, 1.10–1.50).

The researchers explained that while precise biological mechanisms through which repeated antibiotic use may increase the ALS risk are unclear, the altered gut microbiome may play a role. This is in light of evidence showing a profound impact of the gut microbiota on the central nervous system in both neurodevelopmental and neurodegenerative diseases. [Cell 2016;167:915-932]