Effect of Probiotics on Psychiatric Symptoms and Central Nervous System Functions in Human Health and Disease: A Systematic Review and Meta-Analysis

Abstract

Background: The gut microbiota impacts on central nervous system (CNS) function via the microbiota-gut-brain axis. Thus, therapeutics targeting the gut microbiota such as probiotics have the potential for improving mental health. This meta-analysis synthesizes the evidence regarding the impacts of probiotics on psychological well-being, psychiatric symptoms and CNS functioning.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied for executing this review using the databases PubMed, Web of Science and Cochrane Library. The data were summarized at qualitative and quantitative level.

Results: Fifty-four randomized placebo-controlled studies were included, of which 30 were eligible for meta-analysis. If investigated, the probiotics mostly exerted effects on CNS function. Most probiotics did not affect mood, stress, anxiety, depression and psychiatric distress when compared to placebo at the qualitative level. At quantitative level, depression and psychiatric distress improved slightly in the probiotic condition (depression: mean difference -0.37 (95% CI: -0.55, -0.20); p ≤ 0.0001; psychiatric distress: mean difference -0.33 (95% CI: -0.53, -0.13); p = 0.001).

Conclusions: To date it is unclear to which extent and in which specific areas next generation probiotics selected and developed for their ability to improve psychiatric condition and potentially other CNS functions are promising.

Keywords: anxiety; central nervous system (CNS); depression; meta-analysis; mood; paraprobiotics; probiotics; psychiatric distress; stress; systematic review.

Figure 1

PRISMA flow chart for study inclusion.

Figure 2

Study outcomes at qualitative level for the most used questionnaires compared between probiotic versus placebo intervention. ↔: no significant differences between the groups; ↑: improvement p < 0.05; ↑↑: improvement p < 0.01; ↑↑↑: improvement p < 0.001; BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; DASS-42: Depression, Anxiety and Stress Scale; GHQ: General Health Questionnaire; HADS-A/-D: Hospital Anxiety and Depression Scale; HAM-A: Hamilton Anxiety Rating Scale; HAM-D: Hamilton Depression Rating Scale; LEIDs: Leiden index of depression severity; POMS: Profile of Mood States; PSQI: Pittsburgh Sleep Quality Index; PSS: Perceived Stress Scale; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; SCL90: Symptoms Checklist-90; STAI: State Trait Anxiety Inventory.

Figure 3

Study outcomes at qualitative level for the studies included in the meta-analysis. Comparison between the probiotic and placebo group [20,30,32,33,37,38,41,42,44,45,46,47,48,49,51,52,55,57,58,63,64,66,67,68,69,70,71,72,77,78]. ↔: no significant differences between the groups; ↑: significant improvement in the probiotic group versus placebo p < 0.05; ↑↑: significant improvement in the probiotic group versus placebo p < 0.01.

Figure 4

Quantitative analysis for Profile of Mood States (POMS) of randomized controlled trials receiving either probiotics or placebo treatment. Murata 2018 [54], Ohsawa 2018 [58], Sashihara 2013 [69], Shinkai 2013 [72].

Figure 5

Quantitative analysis for Perceived Stress scale (PSS) of randomized controlled trials receiving either probiotics or placebo treatment. Chung 2014 [36], Messaoudi 2011 [52], Östlund-Lagerström 2016 [59], Patterson 2020 [60], Sanchez 2017 [68].

Figure 6

Quantitative analysis for anxiety of randomized controlled trials receiving either probiotics or placebo treatment. Eskandarzadeh 2021 [30], Gualtieri 2020 [42], Ho 2021 [43], Karbownik 2020 [46], Kato-Kataoka 2016 [47], Messaoudi 2011 [52], Nishida 2019 [56], Östlund-Lagerström 2016 [59], Patterson 2020 [60], Raygan 2018 [62], Raygan 2019 [63], Roman 2018 [65], Sanchez 2017 [68], Steenbergen 2015 [73], Takada 2016 [74], Takada 2017 [75], Tran 2019 [76].

Figure 7

Quantitative analysis for depression of randomized controlled trials receiving either probiotics or placebo treatment. Akkasheh 2016 [32], Ho 2021 [43], Kazemi 2019 [48], Messaoudi 2011 [52], Nishida 2019 [56], Östlund-Lagerström 2016 [59], Papalini 2019 [20], Raygan 2018 [62], Raygan 2019 [63], Reininghaus 2020 [64], Roman 2018 [65], Rudzki 2019 [67], Sanchez 2017 [68], Steenbergen 2015 [73], Zhang 2021 [79].

Figure 8

Overview of psychiatric distress symptom outcomes according to questionnaire. Gualtieri 2020 [42], Messaoudi 2011 [52], Mohammadi 2016 [53], Nishida 2019 [56], Nishihira 2014 [57], Raygan 2018 [62], Reininghaus2020 [64], Rudzki 2019 [67].