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Page 14 of 19 Misera et al. Microbiome Res Rep 2024;3:48 https://dx.doi.org/10.20517/mrr.2023.81

depression-like (Exp 1) and n = µg/200 µL), daily immunohistochemistry increased open arm entries (EPM), modulating the gut microbiota, females are
behavior 72 (Exp 2) for 2 weeks decreased immobility (TST, FST) increasing 5-HT levels, and unknown
ELISA: increased 5-HT in serum and affecting the BDNF/TrkB Short duration of
hippocampus, decreased signaling pathway intervention
corticosterone The potential
qRT-PCR: increased BDNF, TrkB, impacts of
GFAP, c-Fos in hippocampus antibiotic-induced
16S rRNA gene sequencing: altered gut microbiota
gut microbiota composition changes on overall
Immunohistochemistry: increased health are not fully
MUC2 expression explored

A. muciniphila: Akkermansia muciniphila; CRS: chronic restraint stress; DSS: dextran sodium sulfate; CFU: colony-forming unit; OFT: open field test; TST: tail suspension test; FST: forced swimming test; ELISA: enzyme-
linked immunosorbent assay; qRT-PCR: quantitative real-time polymerase chain reaction; 16S rRNA: 16S ribosomal RNA; PAS/AB: periodic acid-Schiff and Alcian blue; BDNF: brain-derived neurotrophic factor; DEGs:
differentially expressed genes; CUMS: chronic unpredictable mild stress; 5-HT: 5-hydroxytryptamine; Tph1: tryptophan hydroxylase 1; DRN: dorsal raphe nucleus; CNS: central nervous system; MGBA: microbiota-
gut-brain axis; PFC: prefrontal cortex; SPT: sucrose preference test; CAE: chronic alcohol exposure; LDB: light/dark box test; EPM: elevated plus maze; TrkB: tropomyosin receptor kinase B; GFAP: glial fibrillary acidic
protein, c-Fos: cellular proto-oncogene fos.

pasteurized A. muciniphila MucT (commercially available strain) at a dose of 10 TFU/day for three months may favorably affect gut microbiota and increase
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intestinal barrier integrity, which will lead to reduced inflammation and negative health effects of stress in healthy participants.

Another very interesting application of pasteurized A. muciniphila MucT is reducing stress in overweight and obese individuals. A proof-of-concept clinical

trial showed that pasteurized A. muciniphila MucT improved insulin sensitivity and reduced insulinemia and plasma total cholesterol levels.

In addition, reductions in body weight (without lifestyle or diet modifications permitted), fat mass, and hip circumference were observed compared to those of
the placebo group. After three months of supplementation with this postbiotic, a reduction in blood markers of liver dysfunction and inflammation was also

observed . The relationship between stress, obesity, and diet is very complex. It has been historically known that stress disturbs cognitive processes, among
[103]
them executive function and self-regulation. Stress can induce overeating (and elevates leptin, ghrelin, and neuropeptide Y), increase the propensity to choose
unhealthy food, and reduce physical activity and sleep, which are critical life behaviors in maintaining health.

Finally, stress activates the HPA and impact-reward processing in the brain and the gut microbiome composition. Complicating matters further, obesity itself

can be a stressful condition due to the high prevalence of weight stigma . Therefore, pasteurized A. muciniphila MucT may be a valuable component of stress
[104]
therapy in overweight and obese individuals. Confirmation of this thesis requires more robust clinical research.