Shan Liang

Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress

Increasing numbers of studies have suggested that the gut microbiota is involved in the pathophysiology of stress-related disorders. Chronic stress can cause behavioral, cognitive, biochemical, and gut microbiota aberrations. Gut bacteria can communicate with the host through the microbiota-gut-brain axis (which mainly includes the immune, neuroendocrine, and neural pathways) to influence brain and behavior. It is hypothesized that administration of probiotics can improve chronic-stress-induced depression. In order to examine this hypothesis, the chronic restraint stress depression model was established in this study. Adult specific pathogen free (SPF) Sprague-Dawley rats were subjected to 21 days of restraint stress followed by behavioral testing (including the sucrose preference test (SPT), elevated-plus maze test, open-field test (OFT), object recognition test (ORT), and object placement test (OPT)) and biochemical analysis. Supplemental Lactobacillus helveticus NS8 was provided every day during stress until the end of experiment, and selective serotonin reuptake inhibitor (SSRI) citalopram (CIT) served as a positive control. Results showed that L. helveticus NS8 improved chronic restraint stress-induced behavioral (anxiety and depression) and cognitive dysfunction, showing an effect similar to and better than that of CIT. L. helveticus NS8 also resulted in lower plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, higher plasma interleukin-10 (IL-10) levels, restored hippocampal serotonin (5-HT) and norepinephrine (NE) levels, and more hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression than in chronic stress rats. Taken together, these results indicate an anti-depressant effect of L. helveticus NS8 in rats subjected to chronic restraint stress depression and that this effect could be due to the microbiota-gut-brain axis. They also suggest the therapeutic potential of L. helveticus NS8 in stress-related and possibly other kinds of depression.

Lactobacillus fermentum NS9 restores the antibiotic induced physiological and psychological abnormalities in rats

Gut microbiota play a vital role in maintaining the health of the host. Many factors affect gut microbiota; application of broad range antibiotics disturb microbiota, while probiotic application protects the microbiota. To investigate how probiotics alter the physiological and psychological changes induced by antibiotics, we tested the performance of ampicillin-treated rats in the presence or absence of Lactobacillus fermentum strain NS9, in elevated plus maze and Morris water maze. The results showed that NS9 normalised the composition of gut microbiota and alleviated the ampicillin-induced inflammation in the colon. The levels of the mineralocorticoid and N-methyl-D-aspartate receptors were also elevated in the hippocampus of the ampillicin+NS9 treated group. NS9 administration also reduced the anxiety-like behaviour and alleviated the ampicillin-induced impairment in memory retention. These findings suggest that NS9 is beneficial to the host, because it restores the physiological and psychological abnormalities induced by ampicillin. Our results highlight how gut contents regulate the brain, and shed light on the clinical applications of probiotics to treat the side effect of antibiotics and mental disorders.

Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features

The aim of this study was to compare the structure of gut microbiota in Parkinson’s disease (PD) patients and healthy controls; and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia (P=0.018), Faecalibacterium (P=0.048) and Ruminococcus (P=0.019) were significantly decreased in PD compared to healthy controls. The putative pathobionts from the genera Escherichia-Shigella (P=0.038), Streptococcus (P=0.01), Proteus (P=0.022), and Enterococcus (P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.

Antibiotic-induced imbalances in gut microbiota aggravates cholesterol accumulation and liver injuries in rats fed a high-cholesterol diet

Increasing evidence suggests that maintenance of homeostasis between gut microbiota and host plays an important role in human health. Many diseases, such as those affecting the liver, have been linked to imbalances in gut microbial communities. However, it is not clear whether an imbalance in gut microbiota promotes the onset of liver injury or if the imbalance results from the pathological state. In the current study, antibiotics were used to disturb the gut microbiota of both rats fed a high-cholesterol diet and rats fed a normal diet (controls). The prevalence of Bacteroidetes and Firmicutes were reduced, and Proteobacteria was greatly increased in the guts of rats after antibiotic treatment. The antibiotic-induced perturbation of gut microbiota aggravated cholesterol accumulation and liver injury in rats fed a high-cholesterol diet. This may have been due to an increase in intestinal permeability and plasma lipopolysaccharide (LPS), which lead to an increase in LPS absorption and activation of TLR4 signaling, resulting in the synthesis of pro-inflammatory cytokines and chemokines in liver tissues. This study suggests that imbalances in gut microbiota may be a predisposing factor for the onset of metabolic diseases and liver injuries related to cholesterol and high-cholesterol diets. Modulation of gut microbiota could be a novel target for preventing cholesterol-related metabolic disorders.

Microorganism and Behavior and Psychiatric Disorders: Microorganism and Behavior and Psychiatric Disorders

As we know that some pathogenic microorganisms not only influence host brain and behaviors,but also cause psychiatric disorders.Recent researches indicate that beneficial symbiotic microorganisms,which also known as probiotics,may improve host health both physically and mentally.Gut microorganisms are involved in the development of the neural system and behavioral pattern of mice.They are also related to chronic gastrointestinal disorders and chronic fatigue syndrome.Some central nervous system diseases,such as hepatic encephalopathy and multiple sclerosis may be induced by the disturbance of gut micro-ecosystems.Depression and autism also may be related to the status and proportion of gut microorganisms.The observations above are consistent with the hygiene hypothesis.Balanced symbiotic microorganisms could play an important role in human physical and mental health.Although the mechanisms still remain to be clarified,various hypotheses and research models will give us a better understanding of the role of gut-brain axis in host health.We believe that the relation of symbiotic microorganisms and host health will become a promising research subject in psychology.

Recognizing Depression from the Microbiota–Gut–Brain Axis

Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain–gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota–gut–brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain–gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders.

Gut-Brain Psychology: Rethinking Psychology From the Microbiota–Gut–Brain Axis

Mental disorders and neurological diseases are becoming a rapidly increasing medical burden. Although extensive studies have been conducted, the progress in developing effective therapies for these diseases has still been slow. The current dilemma reminds us that the human being is a superorganism. Only when we take the human self and its partner microbiota into consideration at the same time, can we better understand these diseases. Over the last few centuries, the partner microbiota has experienced tremendous change, much more than human genes, because of the modern transformations in diet, lifestyle, medical care, and so on, parallel to the modern epidemiological transition. Existing research indicates that gut microbiota plays an important role in this transition. According to gut-brain psychology, the gut microbiota is a crucial part of the gut-brain network, and it communicates with the brain via the microbiota–gut–brain axis. The gut microbiota almost develops synchronously with the gut-brain, brain, and mind. The gut microbiota influences various normal mental processes and mental phenomena, and is involved in the pathophysiology of numerous mental and neurological diseases. Targeting the microbiota in therapy for these diseases is a promising approach that is supported by three theories: the gut microbiota hypothesis, the “old friend” hypothesis, and the leaky gut theory. The effects of gut microbiota on the brain and behavior are fulfilled by the microbiota–gut–brain axis, which is mainly composed of the nervous pathway, endocrine pathway, and immune pathway. Undoubtedly, gut-brain psychology will bring great enhancement to psychology, neuroscience, and psychiatry. Various microbiota-improving methods including fecal microbiota transplantation, probiotics, prebiotics, a healthy diet, and healthy lifestyle have shown the capability to promote the function of the gut-brain, microbiota–gut–brain axis, and brain. It will be possible to harness the gut microbiota to improve brain and mental health and prevent and treat related diseases in the future.

Gut microbiota and autism

Autism spectrum disorder (ASD) is one of the most severe neurodevelopmental disorders in the world, and it has brought tremendous burden for family and society. However, there is still no effective method clinically to cure this disorder. The morbidity of the disorder has increased rapidly in recent decades, which does not correspond with Hardy-Weinberg Equilibrium, indicating the disorder is more involved in some environmental factors than genes. Maternal disturbances, poor diet, and leaky gut are remarkable risk factors for autism, all of which can induce gut microbiota dysbiosis. More and more studies have indicated that autism is closely related to imbalanced gut microbiota and abnormal gut-brain axis. Autistic children have different gut microbiota including bacteria and fungi from healthy children, and gut microbiota modulation using either antibiotics, probiotics, or fecal microbiota transplantation may change autistic symptoms. Due to the synchronization of gut brain development and brain development, factors that affect the gut microbiota development of infants during the critical period will increase the incidence rate of autism. Gut microbiota can influence brain development and brain function like behavior and cognition through gut-brain axis/microbiota-gut-brain axis. The microbiota-gut-brain axis mainly include four pathways, which are metabolism, immune system, neuroendocrine system, and vagus nervous system. Abnormal microbiota can increase the harmful metabolites including 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) and 4-ethylphenylsulfate (4EPS) to induce autistic-like behaviors. Gut microbiota regulates the development and function of immune system, and microbiota dysbiosis can result in chronic inflammation to impair the normal development of brain and mentality. Abnormal microbiota can induce autistic symptoms through neuroendocrine pathway, it probably disturbs the development and function of hypothalamus-pituitary-adrenal (HPA) axis, influence the activity of serotonergic system and oxytocin system, and increase the content of harmful gas neurotransmitters such as hydrogen sulfide (H2S) and ammonia (NH3). Microbiota dysbiosis can also lead to autistic-like behaviors through vagus nervous system. Gut microbiota dysbiosis will possibly be the effective target of autism treatment. Increasing studies have shown that gut microbiota restoration including probiotics supplementation alleviates autism symptoms. Certain beneficial microbial strains can recover normal microbiota, prevent pathogen infection, alleviate gut barrier leakiness, prompt gastrointestinal function, and improve behavior and cognition development. These beneficial bacteria probably alleviate autism through regulating the microbiota-gut-brain axis function. They can improve brain function via vagus nervous systems, alleviate brain inflammation through immune response regulation, and restore normal brain neurotransmitters and neurogenesis through HPA function recovery and neurotransmitters metabolism regulation. The new intervention is different from traditional interventions which usually focus on one or two symptoms of autism, it not only restores normal gut microbiota but also improve the whole microbiota-gut-brain axis function including the gut brain and the great brain. Certain symbiotic microorganism intervention will probably become promising auxiliary treatment for autism. In the present paper, we review and summarize some valuable related researches between autism and gut microbiota, to provide an important reference for comprehensive prevention and treatment of autism in China.