4. Discussion
Irritable Bowel Diseases [Finally, in this study, psychological distress, anxiety, blindness
DISEASE, BLINDNESS
In this randomized, double-blind placebo-controlled trial with healthy adults, we found no significant effect of probiotics on a set of psychological measures of well-being, anxiety, emotional regulation, interoception, and mindfulness in a general population sample qualified as otherwise healthy. However, further analyses revealed there was a relevant role of lifestyle behaviors concerning both overall mental health and probiotic effectiveness. Healthy Behaviors (HB) was positively correlated with well-being questionnaires while negatively correlated with anxiety and negative affect. Moreover, the interaction between high scores in HB and probiotic intake was the single significant predictor of positive effects on anxiety, difficulties in emotion regulation, and mindfulness in the post-treatment outcomes when controlling for sex and age.Our study contributed to expanding the evidence on the gap concerning the effect of probiotics on mental health in healthy volunteers. Furthermore, our analyses identified variables influencing individual variation in response to treatment. Several meta-analyses point that there is still a lack of evidence for reaching strong conclusions about the efficacy of psychobiotics in healthy volunteers [In our research, higher scores on our HB construct were significantly correlated with higher levels of well-being and lower levels of anxiety across our set of measures. Our study confirms previous findings about strong correlations between lifestyle factors and mental health [Although research on healthy lifestyles commonly addresses diet, exercise and substance misuse, to study microbiome dynamics, environmental exposures should be considered [Overall, our correlational results strongly support the growing body of evidence pointing to the relevance of diet and other lifestyle habits on mental health treatments, in line with the approaches of nutritional and lifestyle psychiatry [When considering the whole population, we observed no significant difference between groups on well-being or emotional regulation and anxiety. This observation is in line with recent meta-analyses conclusions identifying inconsistent effects of probiotics regarding pooled meta-analytic outcomes and denoting the need for further research to determine appropriate dosage, strains, and intervention duration between healthy and clinical samples [It is possible that insufficient sample size or intervention duration have played a role in the apparent lack of effect when considering the whole population. It is also possible, as our exploratory analyses suggest, that our broad notion of “healthy volunteers” and our inclusion and exclusion criteria did not define a sufficiently specific sample. We discuss this in the following section. It is also relevant to note that this randomized clinical trial was done in the early stage of the COVID-19 pandemic in Chile. This period has been associated with high levels of psychological distress among Chileans, especially in women [The same probiotic formulation we tested has previously shown potential to exert anti-stress and anti-anxiety effects on healthy subjects [A way to enhance probiotic effectiveness is the combination of probiotics and prebiotic compounds, under the concept of ‘synbiotic’ [Our findings are also in agreement with previous interventional research showing a high level of inter-individual variability in the response to probiotics [Lifestyle habits such as diet, exercise, and smoking are established determinants of health [All in all, there are reasons to extend lifestyle characterization of trial participants to other mental health interventions, such as psychopharmacology, psychotherapy, and other evidence-based interventions, for example, mindfulness-based stress reduction programs. Previously, controlling for lifestyle patterns in mental health research has been proposed as a way to face the problem of heterogeneity of outcomes in clinical trials concerning mental health [Interestingly in this line, the positive effects on mindfulness traits as measured by FFMQ represent a novel finding. The literature linking mindfulness and the microbiota-gut-brain axis is scarce. Moreover, the focus of existing research relates to top-down processes, i.e., the potential benefit of mindfulness practices on Irritable Bowel Diseases [Finally, in this study, we hypothesized that the impact of microbiome modifications on psychological functioning may be modulated by people’s lifestyle. We did so grounded in previous theoretical proposals that approach the complex relationships between the mind, physiological conditions and environmental conditions as a way to accomplish a more integrative view of cognition and therefore of mental health. Our findings show that indeed the effects of the tested psychobiotic formula were potentiated by healthy behaviors in each individual, which are associated with specific microbiome and immunological signatures. Moreover, without considering this behavioral condition of the participant´s physiology, there appeared to be no significant effects of the treatment. In addition to that, we identify a need for further assessing macro-societal factors influencing health perception and general well-being of the participants (e.g., COVID). It is important to develop methodological designs and viable assessment tools to be able to account for these constituent factors of health and cognition.There are some limitations that should be highlighted in order to improve future research and motivate scientific transparency. First, our sample was predominantly women, which had been identified as a predictor of higher psychological distress in this time period [Several strengths can be also identified. First, this study has a strong study design in terms of randomization and blindness which allowed us to reach valid conclusions. Second, this is the first study –to the best of our knowledge– that considers a possible interaction between probiotics and healthy lifestyle behaviors, opening a huge window to future research within the area and outside of it. Additionally, there was a high adherence and low drop out in both groups (See The findings of this study support the notion that lifestyle behaviors are important factors that may modulate psychobiotics effectiveness on anxiety and emotional regulation. Therefore, it is crucial to control these behavioral variables in future studies, both as a way to identify the specific populations that can benefit the most from psychobiotic treatments and as a way to advance existing knowledge about the role of MGBA dynamics upon mental health and disease. We also identify a need to take more into account biological and physiological parameters such as microbiota composition index and lifestyle behavioral patterns in other subfields of mental health research and practice.There are several implications of our results aside from the already mentioned need to better control for lifestyle in clinical trials. As we have discussed, lifestyle patterns are relevant both to psychological outcomes and to psychobiotic treatment response. From the clinical practice perspective, our results support the emphasis of recent psychiatry guidelines [Overall, we found preliminary data that highlight how psychological functioning is dependent upon participant’s lifestyle behavioral patterns. Moreover, our exploratory analyses suggest a bottom-up influence of psychobiotics on anxiety, emotional regulation, and mindfulness traits and interestingly, this effect was dependent on the level of adherence to healthy behaviors. Our results demonstrate the need for controlling for lifestyle variables as a standard practice in human microbiome research and mental health research in general. These findings are also in accordance with an embodied account of psychological states that could support future interdisciplinary developments in mental health research and clinical practice.