Structural disruption of gut microbiota is closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). Previous research has demonstrated that both curcumin (CUR) and metformin (MET) have a therapeutic effect against NAFLD and play a role in modulating the gut microbiota. However, there is a lack of direct comparison between the two medications in terms of the therapeutic efficacy and the regulatory effect on gut microbiota. In this study, we administered either CUR or MET to rats with high-fat diet (HFD)-induced obesity to observe changes in body parameters, biochemical parameters, liver, and ileum pathology and gut microbiota, and used next generation sequencing and multivariate analysis to evaluate the structural changes of gut microbiota in a NAFLD rat model before and after CUR and MET intervention. It was found that both CUR and MET attenuated hepatic ectopic fat deposition, alleviated inflammatory factors, and improved intestinal barrier integrity in HFD-fed rats. More importantly, CUR and MET reduced the Firmicutes/Bacteroidetes ratio and reverted the composition of the HFD-disrupted gut microbiota. Both CUR and MET treatments effectively modified the gut microbiome, enriched the abundance of beneficial bacteria and reduced opportunistic pathogens in obese rats. The abundance of Butyricicoccus was increased while the abundance of Dorea was decreased in HFD + CUR group. Besides, some beneficial bacteria such as Prevotella were increased in MET-treated animals. Spearman’s correlation analysis showed that Helicobacter, Akkermansia, Desulfovibrio, Romboutsia, Corynebacterium, Lactobacillus, Ruminococcaceae_unclassified, Lachnospiraceae_unclassified, and Clostridiales_unclassified showed significantly positive correlations with TG, TC, LDL-C, GLU, IL-6, IL-1β, and TNF-α, and negative correlations with HDL-C (both p < 0.05). However, Prevotella and Stomatobaculum showed an opposite trend. In summary, CUR and MET showed similar effects in alleviating hepatic steatosis, improving intestinal barrier integrity and modulating gut microbiota in HFD-induced obesity rats, and therefore may prove to be a novel adjunctive therapy for NAFLD.

Postpartum depression (PPD) is a mental disorder that affects pregnant women around the world, with serious consequences for mothers, families, and children. Its pathogenesis remains unclear, and medications for treating PPD that can be used during lactation remain to be identified. 919 syrup (919 TJ) is a Chinese herbal medicine that has been shown to be beneficial in the treatment of postpartum depression in both clinical and experimental studies. The mechanism of action of 919 TJ is unclear. 919 syrup is ingested orally, making the potential interaction between the drug and the gut microbiome impossible to ignore. We therefore hypothesized that 919 syrup could improve the symptoms of postpartum depression by affecting the structure and function of the intestinal flora, thereby altering hippocampal metabolism. We compared changes in hippocampal metabolism, fecal metabolism, and intestinal microflora of control BALB/c mice, mice with induced untreated PPD, and mice with induced PPD treated with 919 TJ, and found that 4-aminobutyric acid (GABA) in the hippocampus corresponded with PPD behaviors. Based on changes in GABA levels, multiple key gut bacterial species (Mucispirillum schaedleri, Bifidobacterium pseudolongum, Desulfovibrio piger, Alloprevotella tannerae, Bacteroides sp.2.1.33B and Prevotella sp. CAG:755) were associated with PPD. Metabolic markers that may represent the function of the intestinal microbiota in mice with PPD were identified (Met-Arg, urocanic acid, thioetheramide-PC, L-pipecolic acid, and linoleoyl ethanolamide). The relationship between these factors is not a simple one-to-one correspondence, but more likely a network of staggered functions. We therefore believe that the composition and function of the entire intestinal flora should be emphasized in research studying the gut and PPD, rather than changes in the abundance of individual bacterial species. The introduction of this concept of “GutBalance” may help clarify the relationship between gut bacteria and systemic disease.

Depression is one very common mental health disorder which can cause morbidity and mortality if not addressed. Recent studies have provided strong evidence that depression may be accompanied by immune activation, secondary inflammatory reaction, and hyperactivity of the Hypothalamic Pituitary Adrenal (HPA) axis. It is well-known that it takes at least 2 weeks for conventional antidepressants, especially SSRIs (Selective serotonin reuptake inhibitors) to produce effects. To better understand the mechanism of antidepressant effects on depression and subsequently further elucidate the pathogenesis of depression, we selected phytestrogen daidzein (DD) to observe its effects on the depression-like and anxiety-like behavior in two different rodent models of depression which were induced by learned helplessness and chronic mild stress (CMS) and then simultaneous evaluation of the depression-like behavior, the activity of HPA axis, and circulatory cytokines. Our results showed that daidzein attenuated depression-like behaviors through alleviating HPA axis hyperactivity, decreasing the levels of stress-related hormones, and partly rectifying some inflammatory cytokines imbalance in both the rodent models of depression.

Postpartum depression (PPD) is a common mental health problem that causes maternal suffering and various negative consequences for offspring. The pathogenesis of PPD and the causes of consequences for offspring remain largely unknown. Here, we applied RNA sequencing to sequence the whole transcriptomes of peripheral blood mononuclear cells (PBMCs) from PPD patients (Edinburgh Postnatal Depression Scale [EPDS] score ≥13) and control subjects (EPDS = 0). We found that PPD was positively correlated with multiple genes involved in energy metabolism, neurodegenerative diseases and immune response, while negatively correlated with multiple genes in mismatch repair and cancer-related pathways. Remarkably, genes associated with appetite regulation and nutrient response were differentially expressed between PPD and control subjects. Then, we employed a postnatal growth retardation model by repeated immobilization stress (IS) stimulation to maternal mice. The expression of appetite regulation and nutrient response-related genes in the PBMCs of IS mice and in the hypothalamus of their offspring were also affected. In conclusion, this study provides a comprehensive characterization of the PBMCs transcriptome in PPD and suggests that maternal stress may affect appetite regulation and nutrient response in the hypothalamus of offspring mice.

In many countries, nonalcoholic fatty liver disease (NAFLD) has risen to be the leading cause of liver disease, seriously threatening public health, while effective medical treatments are currently limited. 919 syrup (919 T J) is a Chinese herbal medicine, and both clinical and experimental studies have revealed that it can improve liver function. To study whether 919 T J shows a protective effect in a NAFLD rat model and explore its underlying mechanism, with a focus on the NF-κB pathway. Rats were randomly divided into three groups, including a control group, NAFLD group, and 919 T J group (n = 10 each). The control group received a standard diet, and the other two groups were fed a high-fat diet to establish the NAFLD model. From week 10, rats in the 919 T J group were intragastrically administered 919 T J for 4 weeks, and the NAFLD group was administered the same amount of saline. All rats were anesthetized at the beginning of week 14 to collect blood and liver specimens. Serum lipid levels, serum biochemical markers of liver function, and the gene expression levels of IL-1β, TNF-α, CXCL6, CXCR1, SREBP-1c, PPARγ, and NF-κB in the liver were measured. Oil Red O and hematoxylin and eosin staining of the liver was performed to observe pathological changes in the liver. Significant abnormalities in serum lipid levels and serum biochemical markers of liver function were found in the NAFLD group relative to those in the control group. In addition, serious abnormalities were noted in the expression levels of liver inflammatory factors and lipid metabolism-related genes. Treatment of NAFLD rats with 919 T J reduced body weight and food intake and ameliorated the abnormal blood lipid levels and liver function markers. By regulating the NF-κB pathway, 919 T J downregulated the NF-κB-related proinflammatory signals, ameliorating the expression of inflammatory (IL-1β, TNF-α, CXCL6, and CXCR1) and lipid metabolism-related (SREBP-1c) factors in the liver and improving the NAFLD-induced pathological changes in the liver. 919 T J reduces the liver injury, steatosis, and inflammation caused by NAFLD, thus reversing the disease process.

As a manifestation of metabolic syndrome in the liver, non-alcoholic fatty liver disease (NAFLD) has become the top cause of liver disease in many countries. Recent studies have shown that intestinal microbiota disorder plays an important role in the occurrence and development of NAFLD and that regulating intestinal microbiota provides a new option for NAFLD treatment. In addition, research indicates that risk of NAFLD increases as body mass index rises, and interventions that reduce body weight and change diet can help to lower the incidence of NAFLD. Studies have found that 919 syrup may effectively treat NAFLD in rats by improving liver function and lipid metabolism and regulating body weight and feed intake, however, its potential toxicity and the specific mechanism by which it controls this disease require further exploration. This study assesses both the toxicity of 919 syrup and its regulatory effect on the appetite-related Ghrelin pathway and intestinal microbiota of rats with NAFLD. Results indicate that 919 syrup has no obvious side-effects on body weight, feed intake, blood glucose level, hepatorenal function, and liver tissue structure of normal rats. Moreover, 919 syrup can reverse abnormal changes to expression of Ghrelin pathway genes related to appetite in both the brain and stomach and repair alterations to the intestinal microbiota in rats with NAFLD. This herbal medicine is a safe and promising therapeutic drug for the treatment of NAFLD.