H. Pylori Infection May Increase MS Risk But More Studies Are Needed

MS risk due to infection varied depending on the diagnostic method used

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Infection with the stomach bacterium Helicobacter pylori (H. pylori) does not appear to protect against the development of multiple sclerosis (MS), a review study has found.

However, when researchers focused on studies that used microscopic assessments of tissue instead of other diagnostic methods to detect H. pylori, their data suggested that people with an active infection have a higher risk of developing MS than those without it.

These findings highlight the need for larger studies, in which more accurate methods to diagnose active H. pylori infection are used, to draw conclusions on whether the bacterium has a protective or a causative role in MS development, the researchers noted.

The study, “Helicobacter pylori infection and risk of multiple sclerosis: An updated meta-analysis,” was published in the journal Helicobacter.

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Although the causes of MS are unknown, complex interactions between genetic and environmental factors, as well as previous infections with certain viruses, are thought to contribute to the autoimmune disease.

In contrast, exposure to certain infectious agents in childhood may have a protective effect against MS and other autoimmune diseases, according to a theory called the “hygiene hypothesis.”

“There is also been considerable debate as to whether Helicobacter pylori (H. pylori) is involved in development of MS or not,” the researchers wrote.

H. pylori infection linked to peptic ulcers and stomach cancer

About half of the world’s population is estimated to be exposed to H. pylori, a bacterium that infects the stomach, in their lifetime. Infection with H. pylori has been associated with peptic ulcers (sores on the inside lining of the stomach) and stomach cancer.

While some studies have supported the hygiene hypothesis — with early H. pylori infections being linked to a lower MS risk — others have suggested active H. pylori infection may contribute to MS.

Two previous review studies reported a protective role of H. pylori infection against MS. However, these meta-analyses only included studies that had used antibody tests to diagnose H. pylori infection. These tests are not as sensitive as microscopic examinations and cannot distinguish between acute and chronic infections.

With this in mind, a team of researchers in Iran, along with colleagues in the U.S., the Philippines, Germany, and Greece, conducted a more comprehensive meta-analysis that included studies with different diagnostic methods.

They retrospectively analyzed published studies up to Jan. 30 reporting data on the frequency of H. pylori infection in MS patients and healthy people using standard antibody tests, tissue/microscopic analysis, or molecular techniques.

A total of 25 datasets from 22 studies, published from 2007 to 2021, were ultimately included in the meta-analysis.

A total of 10 studies were conducted in the Middle East and North Africa (Iran, Iraq, and Egypt), seven in Europe and North America (Greece, the United Kingdom, and the U.S.), four in the Western Pacific region (Japan, China, and Australia), and one in South-east Asia (India). Iran had the most available studies, with seven datasets.

Of these, 17 datasets reported the frequency of H. pylori infection in a total of 2,606 MS cases and 2,200 healthy controls. Eight datasets comprised mean antibody levels against H. pylori in 861 MS cases and 706 controls.

Among the 17 datasets with prevalence data, 12 used ELISA — a common laboratory test to detect antibodies in the blood — three used other antibody tests, and two used microscopic methods.

Results varied depending on diagnostic method used

Results showed that the pooled frequency of H. pylori infection was 44.1% among people with MS and 46.1% in controls, a difference that did not reach statistical significance. The team noted, however, that there was a high variability between these studies.

In addition, there was no statistical difference between MS patients and controls in terms of mean levels of antibodies against H. pylori.

This suggested that H. pylori infection had no protective effect against MS.

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However, further analyses showed that results varied depending on the diagnostic method used.

Pooled data from studies using ELISA showed a significant protective effect of H. pylori, with the presence of antibodies against the bacterium being associated with a 41% lower risk of MS.

In turn, those using other antibody tests suggested a link between H. pylori infection and a 33% increased risk of MS that did not reach statistical significance.

Analysis of pooled data from studies that used only microscopic methods indicated that the odds of developing MS were 5.75 times greater in people with an active H. pylori infection.

Since microscopic methods represent “the practical gold-standard approach for the detection of active H. pylori infection,” the team wrote, these data suggest that “active H. pylori infection might be a risk factor for development of MS.”

The researchers hypothesized that current H. pylori infection promotes immune responses that may abnormally recognize and attack molecules in the body, and nerve cells, that resemble those of the bacterium, thereby contributing to neurodegeneration.

The findings reveal that there still is not enough data to draw firm conclusions on whether H. pylori infection has a protective or triggering role in MS development, the researchers noted. Large-scale and well-designed studies are needed to clarify this.

“In addition, we suggest further experimental studies with an appropriate animal model to elucidate the underlying mechanisms involved in the association between of H. pylori infection and MS,” the team concluded.

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