On Today’s Practitioner, we’ve been a champion of reporting on the importance of regulating gut bacteria for mood disorders (see our Mood and Microbiome Resource Center here). A review study including 1,500 
participants, published in General Psychiatry, showed that anxiety symptoms might be reduced by taking steps to regulate the microorganisms in the gut using probiotic and non-probiotic food and supplements. It’s the latter, the benefits of non-probiotic food and supplements, such as a dietary FODMAP, that makes this study unique.
Increasingly, research has indicated that gut microbiota can help regulate brain function through the gut-brain axis. A team of researchers from the Shanghai Mental Health Center at Shanghai Jiao Tong University School of Medicine, set out to investigate if there was evidence to support improvement of anxiety symptoms by regulating intestinal microbiota.
The researchers reviewed 21 studies that collectively looked at 1,503 people. Of the 21 studies, 14 chose probiotics as interventions to regulate intestinal microbiota (IRIFs), and seven chose non-probiotic ways, such as adjusting daily diets. The researchers found that probiotic supplements in seven studies within their analysis contained only one kind of probiotic, two studies used a product that contained two kinds of probiotics, and the supplements used in the other five studies included at least three kinds.
- Overall, 11 of the 21 studies showed a positive effect on anxiety symptoms by regulating intestinal microbiota, meaning that more than half (52%) of the studies showed this approach to be effective, although some studies that had used this approach did not find it worked.
- Of the 14 studies that had used probiotics as the intervention, more than a third (36%) found them to be effective in reducing anxiety symptoms, while six of the remaining seven studies that had used non-probiotics as interventions found those to be effective — a 86% rate of effectiveness.
- The studies that used IRIF alone (16 studies) could be divided into two categories: (1) probiotic interventions (11 studies): (A) single probiotic interventions (four studies), and most of the probiotics were Lactobacillus, (B) two studies used two probiotic mixtures: the Swiss Lactobacillus and the long Bifidobacterium mixture, (C) five studies used at least three probiotic mixtures: Lactobacillus, Streptococcus, Bifidobacterium, and so on; (2) five studies conducted non-probiotic interventions, including low FODMAP, short-chain fructooligosaccharides (scFOS), regulating diet, using trans-galactooligosaccharide mixture, and so on.
- 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.
“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:
- The energy source of gut microbiota growth is mainly food. Adjusting 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.
- 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.
- 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.
“We find that more than half of the studies included showed it was positive to treat anxiety symptoms by regulation of intestinal microbiota. There are two kinds of interventions (probiotic and non-probiotic interventions) to regulate intestinal microbiota, and it should be highlighted that the non-probiotic interventions were more effective than the probiotic interventions. More studies are needed to clarify this conclusion since we still cannot run meta-analysis so far.”
The authors say one reason that non-probiotic interventions were significantly more effective than probiotic interventions was possibly due to the fact that changing diet (a diverse energy source) could have more of an impact on gut bacteria growth than introducing specific types of bacteria in a probiotic supplement. Also, some of the studies introduced different types of probiotics, which means they may have fought against each other. Many of the intervention times used may have been too short to significantly increase the abundance of the imported bacteria.
Also, it should be noted that the subjects were either patients with chronic diseases that are comorbid with anxiety symptoms or healthy individuals. Chronic diseases included inflammatory bowel syndrome (IBS), chronic fatigue syndrome (CFS), rheumatoid arthritis (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 colleagues 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.
Most of the studies did not report serious adverse events, and only four studies reported mild adverse effects such as dry mouth and diarrhoea. This is an observational study, and as such, cannot establish cause. Indeed, the authors acknowledge some limitations, such as differences in study design, subjects, interventions and measurements, making the data unsuitable for further analysis. Nevertheless, they say the overall quality of the 21 studies included was high.
CONCLUSION / “In the clinical treatment of anxiety symptoms, in addition to the use of psychiatric drugs for treatment, the researchers say that one 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.”
