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Page 6 of 19 Misera et al. Microbiome Res Rep 2024;3:48 https://dx.doi.org/10.20517/mrr.2023.81

exacerbating the stress spiral. Numerous scientific studies confirm the link between high levels of stress and
the development of mental illnesses. Therefore, a favorable composition of the gut microbiota may be a
factor that helps protect the body from mental decompensation and can contribute to one’s perception and
[35]
tolerance of stress . Overall, the gut microbiota is crucial for the brain-gut axis, affecting physical and
mental processes. It influences brain development, immune responses, and the production of
neuromediators and their receptors, impacting stress resilience.

Stress-induced microbiota alterations and mental health
The significance of stress impact on the composition and function of host gut microbiota has been
demonstrated in several preclinical studies. For example, a decrease in Lactobacillus and an increase in
[45]
Clostridia in mice exposed to different types of stress have been documented. In contrast to studies in
[46]
rodents, human studies are scarce and focus mainly on naturalistic stressors such as academic examinations
or negative events, but they provide conflicting results [47,48] . In one of the recent studies among COVID-19
frontline healthcare workers (FHWs), experiencing stressful events has been associated with a disrupted gut
microbiome for at least half a year. Microbes positively associated with good mental health were
Faecalibacterium spp. and [Eubacterium] eligens group spp., which have anti-inflammatory properties. It
was found that a low abundance of [Eubacterium] hallii group and a high abundance of Bacteroides eggerthii
shortly after frontline work stress exposure were associated with the reappearance of posttraumatic stress
symptoms .
[49]

Numerous scientific papers also confirm the relationship between stress intensity and gut microbiota
composition, a crucial part of the brain-gut axis . It is also known that a specific composition of the gut
[50]
microbiota, different from the healthy population, can be observed in mentally ill patients [51-54] . Thus, since
stress takes part in the pathophysiology of mental illness and simultaneously has an impact on the gut
microbiota, it seems essential to have an in-depth understanding of the gut microbiota as potential
diagnostic and therapeutic options in case of mental disorders. Of note, psychiatric pharmacotherapy causes
significant shifts in gut microbiome balance , which further increases the risk of cardiometabolic
[55]
disorders. The problem becomes further magnified as these effects are one of the main reasons for
discontinuing treatment. Consequently, a high risk of recurrence of symptoms and a renewed disintegration
of life might occur [35,55] .

Scientists have acknowledged the importance of microbiota balance in maintaining the integrity of the
intestinal barrier and overall well-being. Animal experiments provided essential data on how stressful events
affect the gut barrier integrity [56-58] . On the other hand, microbiota maintains gut barrier integrity and affects
the blood-brain barrier (BBB). Microbial alterations, frequently called dysbiosis, might impair the BBB .
[59]
Stress-induced microbiota alterations lead to allostatic disturbances. The term allostasis was formed to
explain the physiological adaptation mechanisms to environmental stressors, which were regulated by
various mediators, including hormones, neurotransmitters, oxidative stress markers, and inflammatory
processes. The short-term mobilization of allostatic mechanisms enables counteraction of negative
outcomes of stress. However, chronic activation of these mediators [allostatic load (AL)] harms human
health. Allostatic overload leads to negative physical and emotional outcomes and has been associated with
mental and somatic disorders, including metabolic and cardiovascular diseases. It was proposed that an
imbalance within gut microbiota might be a consequence of AL [60,61] .

In conclusion, stress alters gut microbiota composition, influencing mental health. Specific microbiota
compositions are linked to mental illnesses, suggesting potential diagnostic and therapeutic options for
mental disorders.