posted on 2021-09-15, 19:41authored byXiaojie Liu, Huanle Liu, Fuxiao Wei, Di Zhao, Yeze Wang, Meng Lv, Sijun Zhao, Xuemei Qin
Constipation
and depression are tightly related and often co-occur
and coexist in clinic. Yet, the relationships and the underlying mechanisms
are still unclear. Fecal metabolomics and network pharmacology were,
for the first time, applied to investigate the potential correlations
from multiple levels including classic behaviors, metabolomics, and
gene targets. The behavioral indicators were analyzed, providing behavioral
correlations at a macrolevel. Besides, fecal samples were analyzed
by nuclear magnetic resonance spectroscopy to screen the shared and
the unique metabolites and pathways, revealing correlations from a
metabolic perspective. Finally, the disease targets and the functional
pathways were obtained via network pharmacology, demonstrating correlations
at the molecular level. The correlations between constipation and
depression were demonstrated and supported by four-level evidence:
(1) general behaviors, (2) gastrointestinal functions, (3) fecal metabolites
and pathways, and (4) common gene targets and functional pathways.
Especially, the correlations of behaviors and common metabolites showed
that metabolites, including choline, betaine, and glycine, were significantly
associated with constipation and depression. Besides, inflammation
and immune abnormalities and energy metabolism were significantly
involved in the mechanisms. The current findings prove the correlations
between constipation and depression, and provide a basis for deeply
understanding the comorbidities of constipation and depression.