Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

Insulin responses to varying hyperglycaemia in newly diagnosed non-insulin dependent diabetic patients.

The effect of varying degrees of hyperglycaemia on insulin secretion was studied in newly diagnosed non-insulin dependent diabetic patients, stratified according to the fasting plasma glucose values. Of the 116 patients studied, 62 were non-obese and 54 obese. Insulin response patterns during 2h oral glucose tolerance test were analysed in comparison with the values in weight matched control subjects and also with respect to the degree of hyperglycaemia. The effect of hyperglycaemia on beta cell secretion differed in obese and non-obese patients. In the non-obese, fasting insulin levels were within normal range even in those with severe hyperglycaemia while the corresponding values in response to glucose stimulation showed a decreasing pattern. In obese patients, even fasting immunoreactive insulin (IRI) value was decreased and with increasing hyperglycaemia the reduction in IRI response to glucose stimulation was of greater magnitude compared to non-obese patients. Thus the modulating effect of obesity on insulin secretion appears to disappear with development of hyperglycaemia. The insulinogenic index was low in all the diabetic patients.

Changes in peripheral insulin concentrations in non insulin dependent diabetes during treatment. Assessment by mathematical applications.

Serum immunoreactive insulin responses to meal stimulus were studied in 20 newly detected non insulin dependent diabetes mellitus patients, following one week of treatment with high carbohydrate, high fibre diet and glibenclamide. Ten patients showed "rapid glycaemic response" i.e. the glycaemic response was good within a week. The rest of them were called "slow responders". The insulin responses were heterogenous. Mathematical calculations using the glucose and insulin responses showed improved beta cell function and peripheral action of insulin in rapid responders. On the other hand, the slow responders showed only slightly improved beta cell function with no change in peripheral action of insulin. The second phase of the study constituted follow-up studies upto 6 months. The corrected insulin response (CIR) increased initially in several patients. The peripheral insulin action improved in all patients with longer duration of treatment and lower insulin concentrations were required to maintain normoglycaemia at this stage. The results of the study indicate that a) multiple factors influence glucoregulation, b) even short term effects of the drug appear to be mediated by extra pancreatic mechanisms, and c) the extrapancreatic action improves significantly on long term use of the drug.

Immunoreactive insulin and insulin degrading enzymes in erythrocytes. A preliminary report.

Immunoreactive insulin (IRI) and insulin degrading enzyme activity (IDEA) of the plasma and the corresponding erythrocyte lysate were estimated in 21 normal volunteers, 18 non insulin dependent diabetic patients (NIDDM), and 16 insulin dependent diabetics (IDDM). The erythrocytes contained several-fold higher concentrations of IRI than in plasma, both in normal and diabetic subjects. The values in controls ranged from 80 to 458 uU/ml against a range of 5 to 25 uU/ml in the corresponding plasma samples. The IRI contents of the diabetic patients were also similar. It showed no correlation to the fasting plasma glucose or the plasma IRI. Following an oral glucose load, no change occurred in the IRI content of the erythrocytes, unlike the changes seen in plasma. The IRI content of the lysate increased with dilution of the sample. The IDEA was higher in diabetic patients compared to controls, especially so in the IDDM (P less than 0.01). It also showed more than one peak activity at different pH of the reaction buffer, indicating the possibility of a complex of enzymes. Human erythrocytes contain large pools of IRI and its degrading enzymes. The significance of the pool of the insulin in non-target tissue needs to be studied.