Abnormal composition of gut microbiota contributes to delirium‐like behaviors after abdominal surgery in mice

Abstract

Summary Aims Anesthesia and surgery can cause delirium‐like symptoms postoperatively. Increasing evidence suggests that gut microbiota is a physiological regulator of the brain. Herein, we investigated whether gut microbiota plays a role in postoperative delirium (POD). Methods Mice were separated into non‐POD and POD phenotypes after abdominal surgery by applying hierarchical clustering analysis to behavioral tests. Fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition among sham, non‐POD, and POD mice. Fecal bacteria from non‐POD and POD mice were transplanted into antibiotics‐induced pseudo‐germ‐free mice to investigate the effects on behaviors. Results α‐diversity and β‐diversity indicated differences in gut microbiota composition between the non‐POD and POD mice. At the phylum level, the non‐POD mice had significantly higher levels of Tenericutes, which were not detected in the POD mice. At the class level, levels of Gammaproteobacteria were higher in the POD mice, whereas the non‐POD mice had significantly higher levels of Mollicutes, which were not detected in the POD mice. A total of 20 gut bacteria differed significantly between the POD and non‐POD mice. Interestingly, the pseudo‐germ‐free mice showed abnormal behaviors prior to transplant. The pseudo‐germ‐free mice that received fecal bacteria transplants from non‐POD mice but not from POD mice showed improvements in behaviors. Conclusions Abnormal gut microbiota composition after abdominal surgery may contribute to the development of POD. A therapeutic strategy that targets gut microbiota could provide a novel alterative for POD treatment.

Antibiotic-induced microbiome depletion protects against MPTP-induced dopaminergic neurotoxicity in the brain

“…Next, we investigated the composition of the gut microbiota, which can be altered by antibiotic cocktail treatment [33–35], in the four experimental groups. α-diversity is defined as the richness of gut microbiota and can be measured using different indices.…”

“…Moreover, although antibiotics are crucial, their overuse plays a role in the pathogenesis of several diseases associated with microbiota impairment [24, 25]. Antibiotic cocktail-induced microbiome depletion has been used to investigate the role of gut microbiota in some pathological conditions [26–35]. In addition, Sampson et al .…”

Ketamine Alleviates Postoperative Depression-Like Symptoms in Susceptible Mice: The Role of BDNF-TrkB Signaling

“…After checking the original data, we concluded that SPT results were more constant than the others, suggesting SPT may be a major factor of the clustering results. Next, our previous study (Zhang et al, 2019) indicated that postoperative delirium was at high risk during early-stage after surgery and anesthesia, in which emotional disorder, such as depression, occurred frequently in clinics (Samuelsson et al, 2007;Costigan et al, 2009;Patel and Sun, 2009). Hence, behavioral tests at early timepoints were suitable to be employed to observe the depressionlike symptoms in mice.…”

Pathomechanisms of Non-Traumatic Acute Brain Injury in Critically Ill Patients

“…This microbial dysbiosis is closely linked to disturbances of gene expression of inflammatory cytokines. It has been documented that abnormal intestinal microbiota composition may be an important risk factor of postoperative delirium [ 93 ]. An experimental study has shown an elevated amount of Escherichia and Shigella in animals with delirium [ 94 ].…”