Influence and Selection of Probiotics on Depressive Disorders in Occupational Health: Scoping Review

Depressive disorders have a major impact on occupational health and are costly to the economy and the healthcare system. Probiotics are live, non-pathogenic micro-organisms that, when ingested in adequate amounts, can colonize the intestinal tract and confer health benefits on the patient. In recent years, numerous studies have described the potential usefulness of certain probiotic strains in the treatment and prevention of depressive disorders, with differing results. In order to evaluate the possible efficacy and safety of these microorganisms in preventing or ameliorating these disorders, we systematically searched the bibliographic databases MEDLINE (via Pubmed), EMBASE, the Cochrane library, Scopus and Web of science, using the descriptors “Occupational health”, “Probiotics”, “Depressive Disorder” and “Depression” and filters “Humans” and “Clinical Trials”. After applying our inclusion and exclusion criteria, 18 studies were accepted for review and critical analysis. Our analysis suggests that a combination of different probiotic strains, most of them from the genus Bifidobacterium sp. and Lactobacillus sp., could be a good mixture as an adjuvant in the treatment of depressive disorders for the working population.


Introduction
The World Health Organization (WHO) assembly proposes to develop national policies and action plans and to create institutional competencies for occupational health, ensuring, in collaboration with other relevant national health programmes, mental health [1]. According to the International Labour Organization (ILO), work helps to maintain good health as long as the worker's physical and mental capacities are not overtaxed [2].
Research shows that health interventions in the workplace can reduce sickness-related absenteeism by 27% and the cost of healthcare for companies by 26% [1]. Globally, 12,000 million working days are estimated to be lost each year due to depression and anxiety, at a cost of USD 1 billion per year in productivity loss. Related health problems in this area cause a loss of GDP (gross domestic product) of between 4 and 6% in most countries. In 2019, an estimated 15% of working-age adults suffered from a mental disorder [1], and the ILO has established a number of occupational illnesses, including mental and behavioural disorders [3].

Microbiota
Microbiota are the set of microorganisms (bacteria, fungi, archaea, viruses and parasites) that reside in our body, which, in turn, can be differentiated into commensals, mutualists and pathogens [17,18]. Microbial communities can be found throughout the human body, the most complex and dense being the one inhabiting the digestive tract and, specifically, the large intestine (gut microbiota). It plays numerous roles in our organism, particularly the maturation and development of the central nervous system (CNS), as well as immune response development and modulation. It is referred to as the "second brain" of humans because of its regulatory effect on the central nervous system through neural, chemical and immune pathways [11,19,20]. Studies of the gut-brain axis (GBA) through the vagus nerve have provided essential insights into the healthy regulation of the hypothalamic-pituitaryadrenal axis (HPA), neuromodulation and neuronal plasticity [21]. This axis forms a network that includes the gastrointestinal tract, the enteric nervous system and the brain [20]. This gut microbiota play an essential role in the regulation of immune, endocrine and metabolic functions. Bacterial metabolites from this microbiota include the short chain fatty acids (SCFAs), made from fermentation of dietary fibre in the gut. Other enzymes and metabolites, such as tryptophan metabolites, gamma-aminobutyric acid (GABA), serotonin, dopamine, norepinephrine, acetylcholine and many neuropeptides, are produced by the microbiota present in the gut [16,19].
Given the ability of many probiotics to function as vehicles for the release of neuroactive compounds, such as classical neurotransmitters, they can be used as an adjunct therapy in the management of neurological disorders. For example, certain strains of Lactobacillus and Bifidobacterium secrete GABA, the main inhibitory neurotransmitter in the brain that regulates affective states, and increases levels of tryptophan, a precursor of serotonin, which suggests it is an antidepressant. The potential of some strains of Lactobacillus to produce acetylcholine, an essential neurotransmitter in several cognitive processes, such as learning and memory, means that they should be included as clear potential coadjuvant treatment, as psychobiotics [16].
Alterations in the gut microbiota, or dysbiosis, lead to a variety of diseases, such as inflammatory bowel disease, coeliac disease, metabolic syndrome, diabetes mellitus, colon cancer, as well as autism spectrum disorder, anxiety and neurodegenerative diseases [20,21]. This dysbiosis, due to increased permeability of the gut microbiota, induces decreased SCFA (short chain fatty acid) synthesis, HPA dysregulation and hypersensitivity of the vagus nerve, which predisposes one to depression [20,21] and, in some cases, to the progression or worsening of major depressive disorders (MDDs) [21].

Probiotics
Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefits on the patient [22]. Recently, the International Scientific Association for Probiotics and Prebiotics [23] established a consensus document with a set of criteria for which microorganisms present in consumer products should be considered as probiotics:

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The microorganism in question must have been scientifically demonstrated to be a safe species that is supported by sufficient evidence of overall beneficial effect in humans.

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Evidence of its viability as a microorganism in human studies must be available.
Several studies [24,25] have proposed the concept of psychobiotics for probiotic bacteria, which, when consumed in adequate amounts, have a beneficial effect on mental health. The mechanisms of action by which bacteria exert their psychobiotic potential have not been fully elucidated. However, it has been found that these bacteria provide their benefits via the enteric nervous system or by stimulating the immune system. In addition, they affect psychophysiological markers of depression and anxiety. This can occur in three different ways: firstly, by affecting the stress response of the HPA axis and reducing systemic inflammation; secondly, through a direct effect on the immune system; and, thirdly, through the secretion of molecules, such as neurotransmitters, proteins and SCFAs [26,27].
Other studies link the intake of probiotics to the prevention and treatment of depression. The work of Bagga et al. [28] examined the clinical relevance of the gut-brain axis with the administration of a multi-species probiotic formulation for four weeks and associated it with changes in brain activation patterns in response to emotional memory tasks and emotional decision making, which were also accompanied by subtle changes in the gut microbiome profile. Akkasheh et al. [29] found that probiotic intake decreased depressive symptomatology as well as oxidative stress levels. In a study by Pirbaglou et al. 2016 [30], an improvement in immune function was observed in those taking probiotics, increasing the number of Natural Killer cells and lymphocytes. This said intake improved the bacterial composition of the gastrointestinal tract and, thus, behaviour and mental health. However, despite these previous works, a review by Vaghef-Mehrabany et al. [31] concluded that current studies are not sufficient to support or reject the antidepressant effects of probiotics.
The different studies on the subject and the differing results obtained only reinforce the belief that not all probiotics are valid, and that it is important to select probiotic strains that can influence the altered physiological processes of the illness targeted by the probiotic product in question [32]. What is important is that the selection of particular strains is based on objective criteria, preclinical studies or plausible hypotheses as to why a specific strain was selected instead of another. In this way, and with the support of clinical studies on the benefit of specific probiotics in specific pathologies, probiotic products can make a significant contribution to the health of the population and, thus, generate cost savings for health systems.
According to the WHO action plan, the loss of economic production due to mental disorders will amount to EUR 16.3 billion between 2011 and 2030. Depression alone accounts for 4.3% of the global burden of illnesses and is one of the leading causes of disability worldwide [33]. Therefore, new treatment options, such as probiotics, could help treat those affected by the illness and contribute to improving the mental health of the general population. Considering publications that demonstrate the benefits of certain probiotic strains in depressive disorders and their ability to stimulate the host's immune response, we set out on this scoping review to identify and select probiotic strains that can prevent depressive disorders, decrease severity in those cases that eventually develop the illness and decrease the impact on occupational health.

Design
We conducted a descriptive study and critical analysis of papers retrieved through exploratory review according to the Preferred Reporting items for Systematic Reviews and Meta-Analyses extension for scoping reviews [34] (Supplementary Table S1).

Data Collection Sources
This review aims to carry out a critical and systematic study of works published on different databases by means of direct consultation and access via Internet to the following databases: MEDLINE (via PubMed), EMBASE, SCOPUS, Cochrane Library Plus and ISI-Web of Science (Institute for Scientific Information).

Information Processing
The document search was defined using the Thesaurus developed by the U.S. National Library of Medicine (Medical Subjects Headings-Mesh). Entry terms were also used. The terms "Occupational health", "Probiotics", "Depressive Disorder" and "Depression" were used as descriptors and free text in title and abstract. The final search equation was developed for use in the MEDLINE database, via PubMed, through the use of Boolean connectors and the filters "Humans" and "Clinical Trial", with the following result: ("Depressive Disorder" (Mesh Terms) OR "Depression" (Title/Abstract) OR "Depressive Disorders" (Title/Abstract) OR "Depressive Symptoms" (Title/Abstract) OR "Emotional Depression" (Title/Abstract) OR ("occupational health" (Mesh Terms) OR "occupational health" (Title/Abstract) OR "Occupational Safety" (Title/Abstract) OR "industrial hygiene" (Title/Abstract) OR "employee health" (Title/Abstract))) AND ("Probiotics" (Mesh Terms) OR "Probiotics" (Title/Abstract) OR "Probiotics" (Title/Abstract) OR "Dietary Supplement" (Title/Abstract) OR "Synbiotic" (Title/Abstract) OR "Microbiota" (Title/Abstract) OR "Microbiotas" (Title/Abstract) OR "Dysbiosis" (Mesh Terms) OR "Dysbiosis" (Title/Abstract) OR "Dysbacteriosis" (Title/Abstract)).
The same strategy was adopted for the other databases mentioned above, taking into account their different characteristics. The search was carried out from the first available date until May 2023 (time of the last update). Additionally, as a secondary search and to reduce the number of papers not retrieved, the bibliographic lists for the articles selected in the main search were examined in order to identify previously undetected studies for the review.

Final Selection of Articles
The final selection of articles was made on the basis of the following inclusion criteria: papers had to be original clinical studies published in peer-reviewed journals, and there had to be a causal relationship between the intake of "probiotics" in "working-age subjects" and with "depressive disorders or "depression", selecting those relevant with full text that could be retrieved, and which had to be written in English, Portuguese or Spanish. We excluded those that were not conducted on humans or that did not focus the intervention on probiotics in people of working age and that had no effect on depressive disorders or depression.
The  [35]. Whenever this condition was met, possible discrepancies would be resolved through consultation with an expert in the field and subsequent consensus among the authors.

Methodological Quality Assessment
The quality of the selected articles was assessed on the basis of the CONSORT (Consolidated Standards of Reporting Trials) guidelines for reporting clinical trials [36], which contain a list of 25 essential items that should be described in the publication of these studies. For each selected article, one point was assigned for each item based on whether the article contained "1" or "0" with regards to the related information. If the evaluation of a particular item was not necessary, that point was not counted in the total (Not Applicable = NA). When an item was made up of several points, these were evaluated independently, giving the same value to each of them and then averaging (this being the final result for that item), so that in no case could the score of one point per item be exceeded.

Data Extraction
The control of the information extracted from the reviewed studies was carried out using double-entry tables that allowed for the detection of errors and correction by further consultation of the originals.
To determine how up to date the articles were, the Burton-Kebler half period (median age) and the Price Index (percentage of articles less than 5 years old) were calculated. The articles were grouped according to the variables under study in order to systematise and facilitate understanding of the results, coding the following data: first author of the bibliographical reference and year of publication, study design, country where the study was carried out, study population, period in which the work was carried out, what type of intervention took place and the results obtained.
The selected papers with the smallest sample sizes were those of Chen et al. [41] and Rode et al. [49], with 11 and 22 participants, respectively. In contrast, the papers by Freijy et al. [42] and Lee et al. [45], with 119 and 122 participants, respectively, presented the largest sample sizes.
The populations studied in the 18 selected studies consisted of people of both sexes. The age of the population included in the studies was between 18 and 65 years, with more or less severe depressive symptomatology [40][41][42][43][44][45]47,48,50,51,54,55], as well as healthy people [38,46,49,52]; of particular note, studies [39,53] focused exclusively on the female population. The follow-up period of the studies included in this scoping review ranged from a minimum of 7 days [52] to 24 weeks [46].
All the selected studies assessed the intake of different specific probiotic strains in the working population and their positive relationship with gut microbiota, biomarkers and clinical symptoms of depressive disorders (anxiety, insomnia, stress, depression, etc.). The species and strains used in the intervention were all Gram-positive, non-sporulating bacteria, and concentrations ranged from 10 6 to 10 10 colony-forming units (CFUs). The studies by Nishida et al. [46], Siegel et al. [52], Freijy et al. [42], Ho et al. [44], Lee et al. [45] and Chen et al. [41] used a capsule as the dosage form, with different amounts between 600 and 1000 mg. In contrast, the pharmaceutical sachet format varying between 1.5 and 5 g was the most commonly used [38,40,43,47,48,50,51,54,55].
The results of the probiotic intervention and its effect on depressive disorders in both healthy and ill subjects were varied. These results are summarized below.

Probiotic Intervention in Healthy Subjects
Bagga et al. [38] demonstrated, in their work, a close relationship between the effects of the intervention with nine probiotic strains and behaviour, reflected in improved functional connectivity (FC) and neuroimaging readings. However, they did not observe any difference in structural connectivity (SC). Bloemendaal et al. [39] observed an increase in the relative abundance of the genus Ruminococcaccae_UCG-003 in the gut microbiota, which correlated significantly with the positive effects of another nine probiotic strains on stress-induced working memory impairment in healthy women.
The work of Siegel et al. [52] and Rode et al. [49] presented similar negative results. In the former, the intervention with the B. longum species did not produce significant changes in improvements or reductions in stress, depression or anxiety in university students. In the latter, results with a mixture of three probiotic strains were subtle in terms of psychological health, depression rates and sleep patterns, as well as markers of gut-brain interactions, such as serum serotonin concentrations. In contrast, Nishida et al. [46] improved stress conditions in young adults with an inactivated probiotic CP2305 intervention, and Smith-Ryan et al. [53] observed a greater reduction in anxiety and fatigue with the intake of nine probiotic strains in female shift workers (nurses, emergency personnel, etc.), although without significant differences when compared with results in the control group.

Probiotics in Patients with Depressive Disorders
Reiter et al. [48] and Reininghaus et al. [47] reported positive results after ingestion of a mixture of nine probiotic strains together with vitamin B7 (biotin) in patients medicated with MDD. The probiotic mixture decreased interleukin 6 (IL-6) gene expression and improved the microbiota with an increase in potentially beneficial bacteria, such as Ruminococcus gauvreauii and Coprococcus 3.
The probiotic mixture of eight different strains together with antidepressant medication was used in the work of Yamanbaeva et al. [54], Schaub et al. [51] and Schneider et al. [55]. The results were prevention of neuronal degeneration along the uncinate fasciculus and alteration of the fronto-limbic rsFC, effects that are partly related to improvements in depressive symptoms, as measured by the Hamilton Rating Scale for Depression (HAM-D) and improvements in verbal episodic memory as well as modulation of neural mechanisms underlying impaired cognition with MDD. These clinical effects were accompanied by the maintenance of a healthy and diverse microbiota with an increase in specific health-related taxa.
With the same mixture of two different strains, the studies of Heidarzadeh-Rad et al. [43] and Romijn et al. [50] presented differing results. The former [43] showed a beneficial effect in improving depression scores compared to placebo. However, the latter [50] found no significant difference between the probiotic and placebo groups in any psychological improvement outcome.
The probiotic strain PS128 significantly improved the severity of depression in patients with MDD [41] and showed significant decreases in Beck's Depression Inventory-II scores, fatigue levels, brain wave activity and awakenings during the deep sleep phase [44]. However, markers of inflammation, gut permeability and gut microbiota composition [41] and improved ANS functionality [44] did not change significantly.
Finally, the results of Chawan et al. [40] with the intervention of nine probiotic strains showed a significantly greater reduction in cognitive reactivity compared to the placebo group, especially in the mild to moderate subgroup, as did the results from the work of Lee et al. [45], where adults with subclinical symptoms of depression, anxiety and insomnia who consumed the NVP-1704 strain experienced a significant reduction in depressive symptoms after four and eight weeks of treatment, and in anxiety symptoms after four weeks, as well as a decrease in serum interleukin-6 (IL6) levels and an improvement in gut microbiota composition.
Other study by Freijy et al. [42], using a symbiotic combination of eight probiotic strains and prebiotics or only probiotics, showed no beneficial results on depressive symptoms. Only the prebiotic-rich diet was beneficial in patients with moderate depressive disorders.

Discussion
The study of the relevance/obsolescence of the chosen topic is quite pertinent and interesting. Out of the total amount of documents retrieved for this review, the majority were published in the last five years; the Burton-Kebler index (BKI) and the Price index (PI), respectively, presented values below the average and above the corresponding values in the area of health sciences. This data demonstrate the full relevance of the topic under study. In health sciences, an IBK of 9 to 12 years and a PI of 33.33% would be expected. [57].
Moreover, according to the degree of evidence and recommendation of the Scottish Intercollegiate Guidelines Network (SIGN) Grading Review Group [58], randomized controlled clinical trials are those that provide the most scientific evidence due to their consistent cause-effect relationship. The quality assessment of the studies included in this review using CONSORT was acceptable, with a mean of 14.8 out of 25. Therefore, the grade of recommendation was B (moderate evidence that the measure is effective and the benefits outweigh the harms).
Furthermore, English is the language of choice for the publication of most articles, which has become common in recent years since publishing in a different language is negative for the impact factor and citations of articles [59]. Moreover, the number of English-language journals available in the databases is currently very high [60].
The Comprehensive Mental Health Action Plan 2013-2030 presents, as main objectives, the implementation of promotion and prevention strategies, the strengthening of information systems, scientific evidence and research [33]. In this research study, we aimed to find out whether the use of probiotics could be an effective contributor to such a promotion and prevention strategy, as well as to improvements in depressive disorders. The 18 selected studies focused on various pathologies, such as anxiety, insomnia and depression. Most of these studies focus on the sick population and therapeutic intervention [40][41][42][43][44][45]47,48,50,51,54,55], while other studies, in a lesser amount, focus on prevention in healthy subjects [38,39,46,49,52,53] of working age.
The systematic review and meta-analysis by Huang et al. [61] confirmed that oral probiotic intake in workers under 60 years of age can effectively reduce scores for depression (Hamilton Rating Scale for Depression HAM-D). In addition, these scores were also improved in the different depressive stages of both healthy subjects and those with depressive symptoms. These data suggest, as concluded in the meta-analysis, that probiotics may be recommended for use in both non-depressed people and patients with depressive disorders. These results occur in the works of Bagga et al. [38], Nishida et al. [46], Smith-Ryan et al. [53] and Bloemendaal et al. [39]. However, the studies of Rode et al. [49], Romjin et al. [50], Siegel et al. [52] and Freijy et al. [42] did not show a significant reduction in improvements in depressive disorders.
The fact that, in the analyzed studies in this exploratory review, at least 28 different strains of bacteria were used successfully, either alone [41,44,46] or in different combinations [38][39][40]43,47,48,51,[53][54][55], suggests that not only one specific strain or a single combination of probiotics will work but that many combinations may be a better treatment option. The use of different probiotic formulations, with no specific strain [52] or two [50] or three [49] probiotic strains alone or high doses of prebiotics [42] may account for the different results observed in these studies concerning improvements in depressive disorders. In selecting the appropriate combination of strains, important factors have to be taken into account, such as the fact that not all combinations are capable of obtaining positive results [32]. In this regard, the combination of Lactobacillus helveticus R0052 (CNCM-I-1722), Lactiplantibacillus plantarum R1012 (CNCM-I-3736) and Bifidobacterium longum R0175 (CNCM-I-3470) [49,50] had barely any effect on improving sleep patterns, depression or on serotonin concentration (biomarker of the gut-microbiota-brain axis). There were also no significant positive results in reducing stress, depression or anxiety with the Bifidobacterium longum intervention [52]. For the very young adult population included in this study, with an average age of 19.5 years, the use of a single species and the fact that the intervention lasted only seven days could be the reason for these weak results. In addition, the dosage used, lifestyle factors and the duration of the intervention could further influence the interpretation of the results [32].
Most of the studies included in this review used a combination of Lactobacillus, Bifidobacterium and/or S. thermophilus or Lactococcus lactis strains. The interventions with probiotic strains in healthy subjects [38,39,46,53] that showed positive results were L. casei W56, L. paracasei W20, L. salivarius W24, L. plantarum W62, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24 Lactococcus lactis W19, Lactococcus lactis W58 and heat-inactivated L. gasseri CP2305 and B. lactis W51, B. lactis W52 and B. bifidum W23. Although the results of the selected studies are not homogeneous, it is once again corroborated that communication between the gut microbiota and the brain is a dynamic process, which can be modulated by a specific (probiotic) intervention, leading to changes in behaviour and brain function [38], and is associated with changes in frontal brain regions during cognitive control and with a microbiota increase in beneficial bacteria such as Ruminococcaccae_UCG-003 [39]. These results are in line with those obtained in clinical studies by Steenbergen et al. [62] and Papalini et al. [63], where a positive correlation was observed between intervention with these probiotic strains and cognition in difficult situations induced by acute stress. These probiotic strains also showed improvements in anxiety and fatigue reduction in female shift workers when combined with the prebiotic W117 [53].
Of particular note is the intervention with the heat-inactivated strain L. gasseri CP2305 and its benefits on young students under stress, with a 24-week treatment period [46]. Similar results were obtained in another study with the same inactivated strain, also including young chronically stressed students and with an intervention period of only 12 weeks [64].
On the one hand, intervention with the combination of 10 probiotic strains together with vitamin B7 in subjects with MDD [47,48] and in people with moderate to severe levels of depressive disorders [40], as well as the L. reuteri NK33 and B. adolescentis NK98 in subjects with subclinical symptoms of depression, anxiety and insomnia [45], improved the plasma levels of proinflammatory cytokines such as IL-6. The latter plays an important role in the pathogenesis of depression, and higher levels were associated with a poor prognosis and worse illness outcome [65,66], as well as with an improvement in negative thought patterns (cognitive reactivity) [40].
Other studies provide results of probiotic intervention on gut microbiota. In particular, an increase in potentially beneficial bacteria, such as Ruminococcus gauvreauii and Coprococcus 3 [47,48], and a decrease in proteobacteria [45] are reported.
Similarly, a combination of eight probiotic strains (Streptococcus thermophilus NCIMB 30438, B. breve NCIMB 30441, B lactis NCIMB 3043, B.lactis NCIMB 30436, L. acidophilus NCIMB 30442, L. plantarum NCIMB 30437, L. paracasei NCIMB 30439 and L helveticus NCIMB 30440), together with antidepressant medication, presented positive results correlating neuronal protection with improvements in depression symptoms (HAM-D), together with changes in bacterial diversity and an increase in healthy bacterial taxa of the gut microbiota. Such probiotics could be a useful additional treatment in MDD or in subjects with symptoms of depression, anxiety and insomnia, due to their anti-inflammatory effects [15,30], and this reinforces the potential microbiota-related treatment approach as one of the accessible therapies in disorders within the sphere of depression.
The studies evaluating the effect of the probiotic composition L. helveticus R0052 (CNCM strain I-1722) and B. longum R0175 (CNCM strain I-3470) presented contradictory results. While in the study by Heidarzadeh-Rad et al. [43], this combination produced beneficial effects on Beck's Depression Inventory (BDI) scores, in the work of Romjin et al. [50], no positive results were obtained with respect to depressive symptomatology. Similarly, the addition of the probiotic strain L. plantarum R1012 to this probiotic composition [49] in healthy subjects also showed no positive results on depression scores, sleep patterns or gut-brain interactions. These results may suggest that these probiotic strains have a greater effect in patients with MDD than in patients with mild symptomatology.
B. bifidum (Bb-06), B animalis subsp. lactis (HN019), B. longum (R0175), L. acidophilus (La-14), L. helveticus (R0052), L. casei (Lc-11), L. plantarum (Lp-115) and L. rhamnosus (HN001) were used as another composition in a study by Freijy et al. [42], where the results showed improvements in mood, anxiety and sleep disorders in adults without a clinical history with the intervention of a prebiotic-rich diet, while the symbiotic mixture (prebiotic plus probiotic) or probiotic alone did not improve mild to moderate psychological disorders in patients with depression. These results should be viewed with caution, as this was not a double-blind study and, therefore, the participants and researchers were not masked in the allocation of the dietary intervention, which could have influenced how participants perceived or reported symptoms, an important bias to consider when assessing the results and information collected in the different forms of Total Mood Disturbances (TMDs), Beck Anxiety Inventory (BAI), etc.
The results of the present review are limited by the shortcomings inherent to each reviewed study [67]. For example, the probiotics selected in the reference papers, as well as the dosage and duration of treatment, are not the same, and other interferences, such as diet and medication, could also have affected the results. Another possible limitation is the small number of articles [44,53] found that specifically assess the impact on occupational health of probiotic intervention on people under stress or with depressive disorders. The depression assessment forms chosen by the different selected studies are not always the same. Moreover, the population studied was not homogeneous (different countries, different diet and different microbiota, shift workers, full-time and part-time workers, students, with mild to moderate and severe depressive disorders, with and without medication, etc.) and, in some cases, the monitoring of the population does not allow the results to be interpreted as strongly as expected.
As a conclusion of this review, and because occupational health is responsible, among other objectives, for the prevention of occupational illnesses among workers, such as anxiety, depression, insomnia, etc., caused by their working conditions [68], these inconclusive results should reinforce the interest of future research on probiotics, and the existing knowledge can serve as a starting point for the selection of strains with functional properties in improvements in depressive disorders. The combination of some probiotic strains that have shown a benefit in mental health could be considered as an adjuvant therapy in the management of mental disorders.

Conclusions
Despite the heterogeneity of the results obtained in the studies included in this review, probiotics may provide an effective adjuvant therapeutic tool to improve mental disorders in adults within the framework of public health. There were virtually no adverse effects in the populations analyzed.