In this study we determined the composition of intestinal microflora in gravidas (who subsequently developed PPD) during 32–39 weeks of gestation. The results showed that the alpha diversity index and the anti-inflammatory bacteria of gut microbiota in gravidas (who subsequently developed PPD) were decreased during 32–39 weeks of gestation compared with healthy pregnant women.
Based on the literature involving human clinical microbiota [9], we identified very few studies with consistent results for depression. In our study patients with PPD had a lower alpha diversity compared with the normal population. Similar to our results, Huang [13] reported that the alpha diversity indices of major depressive disorder were lower than healthy controls. In other studies [14, 15], different results have been presented. Jiang [14] found that patients with active depression had a higher alpha diversity index compared with the normal population. Naseribafrouei [15] did not detect any significant differences in the alpha diversity index.
Acinetobacter is a genus of Moraxellaceae, both of which belong to Pseudomonadales. We observed that all three were increased in PPD. Acinetobacter is a conditionally pathogenic bacteria that is usually associated with respiratory tract infections, accounting for approximately 33.7% of the pathogens causing respiratory tract infections [16]. The researchers also found that the abundance of Acinetobacter is elevated in the gut of patients with neuroinflammatory diseases, such as multiple sclerosis [17]. This association is closely related to the fact that Acinetobacter can induce a proinflammatory response in human peripheral blood mononuclear cells [17]. In a murine study the abundance of Enterococcus was increased in a depression model induced by chronic unpredicted mild stress [18]. This suggests that stress may induce depression by increasing the abundance of Enterococcus. Alloscardovia is a newly discovered genus of Bifidobacterium. The link between Alloscardovia and disease has not been established, but high concentrations of Alloscardovia have been detected in the feces of patients with intrahepatic cholangiocarcinoma, and Alloscardovia may be involved in the metabolism of bile acids [19]. Previous studies have shown that patients with Parkinson disease have a higher abundance of Anaerotruncus in their intestines than healthy individuals [20]. In addition, Anaerotruncus is enriched in the feces of the patients with gestational diabetes mellitus, and negatively correlated with insulin sensitivity [21]. This finding suggests that Anaerotruncus may play a negative role in disease.
Like our results, a reduction in the anti-inflammatory gut microbiota was observed in depressed patients, including Clostridium [22]. Two other studies arrived at an opposite conclusion, with higher levels of clostridia in patients with major depression [14, 23]. The difference in observations may be due to diet. Clostridium can metabolize carbohydrates to produce short-chain fatty acids (SCFAs), and when the intestinal protein is rich, Clostridium will metabolize proteins to produce harmful substances [9]. Patients with major depression may have relatively rich protein remaining in the intestine due to poor appetite, causing Clostridium to grow [9]. We did not include diet in the current study, which was a limitation. In a murine study it has been reported that Clostridium butyricum can modulate inflammatory factors and microglial activation to prevent depression-like behavior [24], which also supports our findings. Butyrate-producing Coprococcus bacteria are consistently associated with higher quality of life indicators. Coprococcus spp. are also depleted in depression, even after correcting for the confounding effects of anti-depressants [25]. Adlercreutzia is an equol-producing bacterium isolated from human feces that contains a single species (Adlercreutzia equolifaciens) [26]. Equol attenuates microglial activation and potentiates neuroprotection in vitro [27]. Animal studies have also shown that equol is beneficial in mitigating depression and anxiety disorders [28]. Lactobacillus and Lactococcus are two common genera of Lactobacillus. Lactobacillus can reduce oxidative stress markers and inflammatory cytokines in the brain and serum to prevent depression [11, 29]. Certain species of Lactococcus can improve depression and anxiety through antioxidant effects [30]. Among the identified species, Clostridium hathewayi can be used as a biomarker for colorectal adenoma and cancer [31], and Enterococcus casseliflavus is a relatively rare enterococcus that causes human infectious diseases, including bacteremia, endocarditis, and meningitis [32]. No studies have found a direct link between Clostridium hathewayi, casseliflavu and depression. Among patients with Behcet’s disease, Megamonas hypermegale may synthesize SCFAs in the intestine and reduce the concentration of SCFAs. These changes will affect the function of the immune system, and thus affect the nervous system [33].
The mechanism underlying the brain-gut axis consists of the interaction of the nervous, endocrine, and immune systems [34]. The inflammation caused by the disorder of intestinal flora and the neuroendocrine hormones produced work together on the intestinal wall, changing the intestinal permeability, and interact with the central system through the vagus nerve. Metabolites produced by intestinal flora (such as SCFAs and tryptophan) can interact with the immune system, changing the body’s immune state and thus changing the brain’s behavior and mood. In addition, an imbalance of neurotransmitters and neuropeptides produced by gut bacteria, such as para-aminobutyrate (GABA), serotonin, and brain-derived neurotrophic factor (BDNF), which act as nerve signaling messengers, can also affect the central nervous system [34].