Main findings
First of all, more than half of the 21 studies included in this paper showed that regulating intestinal flora can effectively improve anxiety symptoms. Of the 14 studies that used probiotics as the intervention, 36% of the studies were effective, while six of the seven studies using non-probiotics as interventions were effective, and the effective rate was 86%. As for the five studies that used the TAU plus IRIF as interventions, only studies that conducted non-probiotic ways were positive; and non-probiotic interventions were also more effective in the studies that used IRIF alone, for 80% of studies could improve anxiety symptoms in the studies that performed non-probiotic interventions while 45% were effective in the studies that used probiotic ways. So we can easily find that although we can regulate the intestinal flora in two ways, the non-probiotic intervention is significantly better than the probiotic intervention. The reasons for this result may be as follows: (A) The energy source of gut microbiota growth is mainly food.24Adjusting the gut microbiota through modulating dietary structure can directly change the energy supplying structure of gut microbiota and this plays a decisive role in the growth of gut microbiota, so the effect is obvious. (B) Although the studies all conducted probiotic interventions, the species of the probiotics were diverse and there were survival competitions in implanted flora and primitive flora, which may lead to not all the imported probiotics being effectively implanted. (C) Most intervention times of included studies were 4–8 weeks. This might be too short to significantly increase the abundance of the imported microbiota, so that the subjects’ original intestinal flora could not be effectively adjusted.
Second, 67% of the studies used probiotic intervention to regulate intestinal flora, while only 33% of the studies used non-probiotic ways such as low FODMAPS, scFOS and supplementary resistance dextrin. On the one hand, this indicates that more and more researchers have realised that microflora plays an increasingly important role in human health, but on the other hand, the function of diets in daily life has been neglected by people. As mentioned above, the effect of dietary structure adjustment is better than that of probiotic supplements. In the future, more attention can be paid to the regulation of intestinal flora through non-probiotic ways, or the combination of probiotic and non-probiotic means, which may have unexpected effects.
In addition, the subjects were patients with chronic diseases comorbid with anxiety symptoms or healthy individuals. Chronic diseases included IBS, CFS, RA, obesity and fibromyalgia. Sixty-seven per cent of chronic disease subjects were patients with IBS, indicating that anxiety symptoms are common in intestinal-related chronic diseases. After reviewing the studies about the pathological mechanism of IBS published in recent years, Raskov and colleagues25 found that the gut-brain axis played a central role in the persistence of IBS and the microbiota played a key role. In the study, the improvement of anxiety symptoms in patients with IBS by adjusting intestinal flora was further evidence of the gut-brain axis mechanism. Last but not least, the vast majority of studies have not reported serious adverse events related to interventions, regardless of what kinds of interventions were conducted. Another point that should be paid attention to was that 67% of six articles about healthy individuals have shown positive effects on anxiety symptoms, this may be strong evidence to support the hypothesis that anxiety symptoms can be relieved by modulating gut microbiota.
Only four studies reported mild adverse reactions such as dry mouth, internal perceptual discomfort and diarrhoea. In summary, more than half of the studies have shown that the intestinal flora could be modulated to alleviate anxiety symptoms and was extremely safe.
Limitations
Due to the differences in the research design types, subjects, interventions and anxiety assessment scales of the 21 articles included, the overall heterogeneity was too large and it was not suitable for meta-analysis. Fifty per cent of the 10 studies on IBS showed that the interventions were effective. Therefore, for patients with IBS, more studies are needed to verify whether it is possible to clinically treat the anxiety symptoms of patients with IBS by regulating intestinal flora. We did not register on PROSPERO whether the individuals had different kinds of diseases or were healthy individuals, rather we recorded all as having the same symptom—anxiety.
Implications
In the clinical treatment of anxiety symptoms, in addition to the use of psychiatric drugs for treatment, we can also consider regulating intestinal flora to alleviate anxiety symptoms. Especially for patients with somatic diseases who are not suitable for the application of psychiatric drugs for anxiety treatment, probiotic methods and/or non-probiotic ways like low FODMAPs can be applied flexibly according to clinical conditions. However, there are still some studies showing that the effect of regulating intestinal flora to improve anxiety symptoms is limited. Therefore, more relevant clinical intervention studies should be carried out with the unified anxiety assessment scales and statistical methods being used to clarify the relationship between intestinal flora adjustment and improvement of anxiety symptoms.