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

energy balance.
5. Peptidoglycan muropeptides activating immune receptors such as nucleotide-binding oligomerization
domain 1 (NOD1) and NOD2, contributing to gut immune responses and maintaining gut health.
6. Membrane lipids (e.g., diacyl phosphatidylethanolamine), which can activate immune receptors like toll-
like receptors (TLR2-TLR1) to induce anti-inflammatory cytokine production.

These modes of action collectively contribute to the beneficial effects of A. muciniphila on gut health,
including enhancing gut barrier function, modulating immune responses, and improving metabolic
conditions.

The psychobiotic potential of A. muciniphila is very promising; however, due to many technological
problems, the administration of probiotics containing this strain is very complicated. For this reason,
technology has been developed to produce pasteurized A. muciniphila, which has comparable or better
properties than the live bacterium and has also been recognized by the European Food Safety Authority
[15]
(EFSA) as a novel food that can be safely administered to humans . As mentioned above, there are
substantial data on the potential use of A. muciniphila in neuropsychiatric disorders; however, little is
known about the effect of this bacterium on stress specifically, which plays a crucial role in the onset of
many neurobiological disorders and has recently become a critical mental health issue . Therefore, in this
[16]
narrative review, we decided to describe the relationship between stress and the microbiota. To achieve this,
we aimed to analyze existing work on the effects of A. muciniphila on stress to organize published
knowledge and guide further research on this topic.

STRESS AND MICROBIOTA
Stress definition and phases
Current psychological descriptions of stress are dominated by the relational view, which states that “stress is
a dynamic relationship between an individual and the environment that is judged by the individual to
require adaptive effort or to be beyond the ability to cope. Recognizing a relationship as stressful is
determined by the subjective evaluation of the individual rather than by the objective properties of the
situation” .
[17]
Stress, in the initial phase, is a highly motivating factor leading to the activation of psychological processes,
mediated by the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adreno-medullar (SAM) axis,
thus enabling effective work on a given problem. On the other hand, prolonged and more severe stress
significantly decreases psychological activities. If this condition persists or if the intensity of the stress
increases rapidly, a so-called destructive phase of stress occurs, in which cognitive and executive functions
[18]
are impaired to a large extent . The perception of stress is a highly subjective process, as is the individual’s
stress resilience. Physiologically, however, the body’s response to stress follows specific patterns explained
[19]
by biochemical pathways and processes . With deeper analysis, it could be theorized that almost any event
or stimulus can be a cause of stress subjectively. Physiological occurrences such as hunger, thirst, sleep
deprivation or hormonal fluctuations can also be stressful for the body. Adding to the complexity, these
stimuli are processed in different regions of the brain. As a response to a perceived stressful situation,
various autonomic nervous system and emotional reactions are triggered [20,21] . In the scope of this review,
stress is defined as a dynamic relationship requiring adaptive effort. Initial stress is motivating, but
prolonged stress decreases psychological activities, leading to impaired cognitive and executive functions.