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Misera et al. Microbiome Res Rep 2024;3:48 https://dx.doi.org/10.20517/mrr.2023.81 Page 11 of 19

reduced the immobility time. In the case of total distance traveled in the OFT and time in open arms in the
elevated plus maze (EPM) test, both treatments showed improvements; however, these were not statistically
significant compared to either control (healthy, vehicle-treated mice) or ABX-treated counterparts. When
gut microbiota was evaluated, it was demonstrated that ACE, Chao, and Simpson indices decreased due to
ABX exposure, with the first ones being recovered with A. muciniphila gavage. The abundance of
A. muciniphila, Firmicutes, Clostridia, and Oscillospiraceae was altered in the ABX group. In the group
treated with A. muciniphila, a significantly higher abundance of Firmicutes and Bacilli was observed. On the
other hand, Amuc_1100 significantly elevated Oscillospiraceae. At the prediction of a functional level,
PICRUSt analyses showed that A. muciniphila/Amuc_1100 alleviated the functions of amino acid transport
and metabolism, coenzyme transport and metabolism, and lipid transport and metabolism diminished with
the ABX cocktail alone. Hippocampal and cortex mRNA expression analyses showed that BDNF and
tropomyosin receptor kinase B (TrkB) increased in the case of A. muciniphila/Amuc_1100 compared to the
ABX group. The latter was significantly higher in the case of Amuc_1100 compared to A. muciniphila. To
add, markers of excessive activation of astrocytes, thus neurotoxicity, glial fibrillary acidic protein (GFAP),
and cellular protooncogen c-Fos mRNA levels were restored in the hippocampus of A. muciniphila and
Amuc_1100 groups.

Finally, 5-HT levels in serum and hippocampus were increased in the case of both interventions as
compared to ABX alone. In contrast, corticosterone levels in serum and mRNA of the glucocorticoid
receptor in the hippocampus decreased. The study confirmed that A. muciniphila and Amuc_1100 diminish
antibiotic-induced anxiety and depression, affecting different parts of the GMBA, including the BDNF/TrkB
signaling pathway and astrocyte activation.

The summary of the above-described studies with their limitations is arranged in Table 1. Based on these
studies, it can be stated that animal studies demonstrate that A. muciniphila has the ability to alleviate stress-
induced behavioral deficits and improve gut microbiota diversity. Mechanisms include interactions with
host receptors and modulation of various stress-related pathways.

Current human studies and applications
To the best of our knowledge, no human studies have evaluated the efficacy of A. muciniphila in alleviating
stress manifestations. One study is ongoing: The Efficacy of Pasteurized A. muciniphila in Healthy Medical
[99]
Workers (MENTAkHEALTH) . Changes in the gut microbiota secondary to chronic exposure to stress
can be a trigger for its manifestation in the form of somatic and psychiatric symptoms. The homeostatic
disturbances and changes in the intestinal bacterial ecosystem initiate a series of inflammatory disorders in
the intestine and the increased synthesis of neurocompetent metabolites, which can negatively affect the
enteric nervous system (ENS) and the CNS as described earlier in this review. Medical professionals are
susceptible to burnout, anxiety, and depression, but also to irregular lifestyles (e.g., shift work) and
[100]
functional disorders of the digestive tract . It was also established that an increasing number of students at
medical universities abide by psychiatric or psychological therapies and thus often take anxiolytics and
[101]
antidepressants . Furthermore, research has shown that the use of antipsychotic drugs, especially of the
second-generation type, can significantly affect the composition of the intestinal microbiota, increasing the
ratio of Firmicutes to Bacteroidetes phyla and affecting the status of A. muciniphila abundance in the
gut . Another ongoing project, funded by the European Union, named Imminent Disease Prediction and
[102]
Prevention at the Environment Host Interface (IMMEDIATE), aims to assess the functioning of the diet-
microbiome-immunometabolism axis, which is the gateway for the initiation of the disease process. An
intervention study using a so-called novel food, i.e., the pasteurized A. muciniphila with potent neuro- and
immunocompetent properties, will evaluate the efficacy of a non-invasive therapy for the homeostasis of
clinical biomarkers and the maintenance of well-being. The researchers hypothesize that administration of