Using antibiotics may increase the risk of developing amyotrophic lateral sclerosis (ALS), with a higher number of prescriptions linked to greater risk, a nationwide study in Sweden suggests.

However, the researchers caution that more studies are needed to prove a direct, cause-and-effect relationship between antibiotics use and ALS.

For the study, titled “ Antibiotics Use and Risk of Amyotrophic Lateral Sclerosis in Sweden, ” researchers investigated the association between antibiotics and the future risk of ALS by comparing the medicine’s use by 2,484 ALS patients, and the general population in Sweden. The report was published in the journal European Journal of Neurology.

Studies in animal models previously suggested that changes in gut bacteria, or gut microbiota, might be associated with ALS. However, results addressing this possibility in humans have been conflicting.

Antibiotics are well known to greatly change the composition of intestinal bacteria. Broad-spectrum antibiotics, for instance, were shown to alter 30% of gut bacteria, reducing their diversity.

Given the impact of these medicines in gut microbiota, the researchers investigated whether individuals who use antibiotics are at a higher risk of developing ALS. The team addressed this question retrospectively, examining data from all prescriptions given since July 1, 2005 in Sweden, using several national health registers.

The researchers investigated how many antibiotics were given to a total 2,484 ALS patients before they were diagnosed with the disease, between 2006 and 2013. This data was compared with prescriptions given 12,420 healthy people, matched by sex, age, and area of residence.

Antibiotics included those used for respiratory infections — amoxicillin, penicillin, cephalosporin, and macrolides — and those prescribed to treat urinary tract and skin and soft tissue infections, including pivmecillinam, sulphonamide, trimethoprim, norfloxacin, ciprofloxacin, nitrofurantoin, flucloxacillin, cloxacillin, and dicloxacillin.

To account for delays in ALS diagnosis, all prescriptions within one year before diagnosis were excluded from the main analysis.

The data showed that people who were prescribed antibiotics, even once, had a slightly higher risk of developing ALS later on.

Moreover, that risk increased with the number of antibiotic prescriptions. The risk was higher for people who had been prescribed the medicine two to three times before, and even greater if they had been given it four times or more.

Similar results were noted regardless of whether the antibiotics were used for respiratory infections, or urinary or skin and soft tissue infections.

However, after specifically examining each type of antibiotics, the investigators found that the risk of ALS was especially increased for those who had received more than two prescriptions of beta-lactamase sensitive penicillins. These penicillins are used to treat more resistant types of some infections.

The researchers found that ALS patients had used antibiotics more often (65.1%) than the general population (61.8%). The increased use among people with ALS was seen as early as six to eight years before diagnosis, and increased sharply over the year immediately prior to diagnosis.

“In conclusion, we found that antibiotics use, especially repeated use, was associated with an increased risk of ALS,” the researchers said.

“The precise biological mechanisms underlying such a relationship remain to be clarified. However, a biological pathway through the altered gut microbiome might be at play,” they added.

Although this was a large, nationwide study, the investigators cautioned that the results are only suggestive, and said more evidence is needed before any cause-and-effect relationship can be claimed.

The study did not account for other potential risk or protective factors for ALS, such smoking, alcohol use and diet.

“[I]t is difficult to disentangle the effect of antibiotics from the effect of the underlying indications for the use of antibiotics, i.e. infections that might be secondary to the underlying ALS disease,” the researchers said.

That means the findings “are only suggestive and cannot prove causality,” they added.

Another important factor, the researchers said, is that the study is based on antibiotics prescribed and dispensed, which does not mean that all people were effectively taking them.