Elderly patients using antibiotics often encounter diarrhea as a side effect, which can sometimes be life-threatening. According to a new study published in The Lancet, probiotic supplements do not appear to reduce the incidence of diarrhea in this group of patients. The study, called the PLACIDE trial, is the largest study to date to evaluate the effects of probiotic supplements on antibiotic-associated diarrhea (AAD) in a real-life setting. Several previous studies have suggested that probiotic preparations may be able to reduce the incidence of AAD, and as a result, prescribing probiotics to elderly patients on antibiotics has become a routine practice in some healthcare settings. However, the exact mechanism by which antibiotics cause diarrhea is not yet fully understood, and it is thought that it may be due to antibiotics disrupting the normal replenishment of “friendly bacteria” in the body. The term “friendly bacteria” refers to the community of microorganisms present in a healthy human digestive system, often referred to as the “gut flora” or “microbiome”. It is thought that probiotic supplements may be able to repair the intestinal flora damaged by antibiotics and restore it to normal, thereby reducing the incidence of AAD. A team of researchers led by Professor Stephen J. Allen of Swansea University in the United Kingdom recruited nearly 3,000 participants for the PLACIDE trial, which was conducted at five hospitals in south Wales and northeast England. All participants in the study were hospitalized patients aged 65 years or older, the age group in which most of the problems caused by AAD occur, and in which patients often require one or more antibiotics. About half of the participants were asked to take one capsule containing a fixed dose of live bacteria (containing two types of Lactobacillus acidophilus, Bifidobacterium bifidum and Bifidobacterium lactis) daily, spaced apart from antibiotics, for 21 days, while the rest were assigned to a placebo control group. Of the patients who developed diarrhea, the researchers analyzed stool samples from nearly half of them to determine whether their gastrointestinal distress was caused by the antibiotics. This analysis also helped the researchers track how many of the participants’ AAD was caused by C. difficile. Diarrhea caused by C. difficile is a particularly serious type of diarrhea that can cause serious, life-threatening infections. Some previous studies have suggested that this type of diarrhea may be best treated with probiotic supplements. However, the researchers found that probiotic supplementation did not appear to reduce the incidence of diarrhea in the experimental group, with both the experimental and control groups reporting an ADD incidence of about one in ten. The frequency and severity of diarrhea occurred similarly in both groups, and the results of quality of life scores for the trial period were comparable between these two groups. In addition, the proportion of diarrhea caused by C. difficile was comparable in both groups, leading the researchers to conclude that there was no evidence to support the claim that patients benefited from the use of probiotic supplements. According to Professor Allen, “Although some studies have concluded that probiotic supplementation reduces the incidence of AAD, those results were mainly from small trials conducted at a single site, and many of them were inconsistent and difficult to meta-analyze. “Our study is the largest study to date on the effects of “probiotic preparations” on AAD, although it may be more appropriate to call them “microbial preparations” because it is uncertain whether they have any health benefits. and the results obtained in this study do not support the use of this class of agents in elderly patients.” Since it is not yet clear how antibiotics cause diarrhea, further research on the effects of microbial agents on AAD is still necessary. Some specific “beneficial” bacteria may indeed have specific anti-diarrheal mechanisms, or the patient’s own disease state, diet and age may alter the effects of probiotic supplements. In a related commentary, Dr. Nick Daneman from the University of Toronto’s Sunning Health Centre noted that although the PLACIDE trial appears to have yielded results that contradict previous meta-analyses, particularly for diarrhea caused by C. difficile, the results are not without merit. He added: “At the very least, this result questions the cost-effectiveness of using probiotics ……PLACIDE is a rigorous large-scale trial that obtained negative results, and we must judge whether this result will change the current probiotic use landscape. “