Gender in Probiotic Use

In this issue, Lönnermark et al¹ report on their study on the effect of probiotic intake, Lactobacillus plantarum, on the clearance of nontyphoid Salmonella and its effect on infection-related symptoms. As women tend to use alternative medicinal therapies more than men,² it behooves us to raise the question as to whether probiotics should be given to both genders equally or in different doses and at different times?² This is an important question that has not been addressed in most studies. This study was conducted at Gothenburg University in the Department of Infectious Diseases. It was a double-blind, placebo-controlled clinical trial. The study analyzed 149 symptomatic patients, of whom 54% were female. The investigators found that probiotic treatment was not effective in accelerating the clearance of Salmonella infection or in reducing acute symptoms. However, they did find differences between male and female patients in terms of clinical symptoms of infection. The study was well designed and well conducted. Feces were cultured weekly. The treatment and placebo groups did not differ significantly with respect to time to clearance of Salmonella or time to resolution of symptoms. Regardless of treatment, women tended to clear Salmonella more rapidly than men, and after clearance women experienced loose stools, nausea, and flatulence more frequently than did men. In women, L. plantarum treatment was associated with greater abdominal pain, whereas in men it increased the presence of diarrhea symptoms in the postinfectious stage. The final conclusion was that gender, but not administration of the probiotic, may influence acute symptoms during Salmonella infection and possibly clearance of Salmonella. What we find important here is that there is a difference in gender symptoms in the postinfectious phase, which were modified by the probiotic. As is pointed out by the authors, Salmonella enterica is an important pathogen in both humans and animals, and there is an estimated global incidence in nontyphoid Salmonella that ranges from 200 million to 1.3 billion patients. However, the persistent gastrointestinal symptoms are quite common after nontyphoid salmonellosis.

What is important here is the marked difference between men and women with respect to clearance of Salmonella and symptoms associated with the infection.^3,4 The authors point out that there is agreement with a previous study showing increased Salmonella-related morbidity in female patients.⁴ In a large study of travelers, women were found more likely to have acute, as well as chronic, diarrhea.⁵ Does persistence of irritable bowel symptoms after salmonellosis represent the first stage of that disorder?³ Variation of symptoms between male and female patients has been questioned previously in the literature.⁶ Those questions have pointed out that the incidence of irritable bowel syndrome is greater in women.⁶

In a controlled, double-blind, randomized study, L. plantarum 299v was shown to be effective in patients with irritable bowel syndrome.⁷ However, a review of the literature has not accepted this concept clinically.⁸

Almost in every phase of clinical medicine gender is an important factor. It is surprising that when we study the literature for probiotic treatment we find so few published studies that mention gender. The literature has interesting papers dating back to 2001 where the long-term consumption of Lactobacillus rhamnosus GG in milk appeared to have beneficial effects on children.⁹ In 2014, a paper reports that L. rhamnosus CG and CGMCC1.3724 help obese women achieve sustainable weight loss, which was more marked than in men.¹⁰

It appears that all of the studies reporting probiotic therapy should now divide their results into gender-specific outcomes.