The role of the gut microbiota and nutrition on spatial learning and spatial memory: a mini review based on animal studies.

The gut-brain axis is believed to constitute a bidirectional communication mechanism that affects both mental and digestive processes. Recently, the role of the gut microbiota in cognitive performance has been the focus of much research. In this paper, we discuss the effects of gut microbiota and nutrition on spatial memory and learning. Studies have shown the influence of diet on cognitive capabilities such as spatial learning and memory. It has been reported that a high-fat diet can alter gut microbiota which subsequently leads to changes in spatial learning and memory. Some microorganisms in the gut that can significantly affect spatial learning and memory are Akkermansia muciniphila, Bifidobacterium, Lactobacillus, Firmicutes, Bacteroidetes, and Helicobacter pylori. For example, a reduction in the amount of A. muciniphila in the gut leads to increased intestinal permeability and induces immune response in the brain which then negatively affects cognitive performances. We suggest that more studies should be carried out regarding the indirect effects of nutrition on cognitive activities via alteration in gut microbiota.

Pharmacological Treatment of Agitation and/or Aggression in Patients With Traumatic Brain Injury: A Systematic Review of Reviews.

OBJECTIVE: To systematically review the available literature on the pharmacological management of agitation and/or aggression in patients with traumatic brain injury (TBI), synthesize the available data, and provide guidelines. DESIGN: Systematic review of systematic reviews. MAIN MEASURES: A literature review of the following websites was performed looking for systematic reviews on the treatment of agitation and/or aggression among patients with TBI: PubMed, CINAHL, DynaMed, Health Business Elite, and EBSCO (Psychology and behavioral sciences collection). Two researchers independently assessed articles for meeting inclusion/exclusion criteria. Data were extracted on year of publication, reviewed databases, dates of coverage, search limitations, pharmacological agents of interest, and a list of all controlled studies included. The included controlled studies were then examined to determine potential reasons for any difference in recommendations. RESULTS: The literature review led to 187 citations and 67 unique publications after removing the duplicates. Following review of the title/abstracts and full texts, a total of 11 systematic reviews were included. The systematic reviews evaluated the evidence for safety and efficacy of the following medications: amantadine, amphetamines, methylphenidate, antiepileptics, atypical and typical antipsychotics, benzodiazepines, ß-blockers, and sertraline. CONCLUSIONS: On the basis of the results of this literature review, the authors recommend avoiding benzodiazepines and haloperidol for treating agitation and/or aggression in the context of TBI. Atypical antipsychotics (olanzapine in particular) can be considered as practical alternatives for the as-needed management of agitation and/or aggression in lieu of benzodiazepines and haloperidol. Amantadine, ß-blockers (propranolol and pindolol), antiepileptics, and methylphenidate can be considered for scheduled treatment of agitation and/or aggression in patients with TBI.

A role for intestinal alkaline phosphatase in preventing liver fibrosis.

Rationale: Liver fibrosis is frequently associated with gut barrier dysfunction, and the lipopolysaccharides (LPS) -TLR4 pathway is common to the development of both. Intestinal alkaline phosphatase (IAP) has the ability to detoxify LPS, as well as maintain intestinal tight junction proteins and gut barrier integrity. Therefore, we hypothesized that IAP may function as a novel therapy to prevent liver fibrosis. Methods: Stool IAP activity from cirrhotic patients were determined. Common bile duct ligation (CBDL) and Carbon Tetrachloride-4 (CCl4)-induced liver fibrosis models were used in WT, IAP knockout (KO), and TLR4 KO mice supplemented with or without exogenous IAP in their drinking water. The gut barrier function and liver fibrosis markers were tested. Results: Human stool IAP activity was decreased in the setting of liver cirrhosis. In mice, IAP activity and genes expression decreased after CBDL and CCl4 exposure. Intestinal tight junction related genes and gut barrier function were impaired in both models of liver fibrosis. Oral IAP supplementation attenuated the decrease in small intestine tight junction protein gene expression and gut barrier function. Liver fibrosis markers were significantly higher in IAP KO compared to WT mice in both models, while oral IAP rescued liver fibrosis in both WT and IAP KO mice. In contrast, IAP supplementation did not attenuate fibrosis in TLR4 KO mice in either model. Conclusions: Endogenous IAP is decreased during liver fibrosis, perhaps contributing to the gut barrier dysfunction and worsening fibrosis. Oral IAP protects the gut barrier and further prevents the development of liver fibrosis via a TLR4-mediated mechanism.

Intestinal alkaline phosphatase targets the gut barrier to prevent aging.

Gut barrier dysfunction and gut-derived chronic inflammation play crucial roles in human aging. The gut brush border enzyme intestinal alkaline phosphatase (IAP) functions to inhibit inflammatory mediators and also appears to be an important positive regulator of gut barrier function and microbial homeostasis. We hypothesized that this enzyme could play a critical role in regulating the aging process. We tested the role of several IAP functions for prevention of age-dependent alterations in intestinal homeostasis by employing different loss-of-function and supplementation approaches. In mice, there is an age-related increase in gut permeability that is accompanied by increases in gut-derived portal venous and systemic inflammation. All these phenotypes were significantly more pronounced in IAP-deficient animals. Oral IAP supplementation significantly decreased age-related gut permeability and gut-derived systemic inflammation, resulted in less frailty, and extended lifespan. Furthermore, IAP supplementation was associated with preserving the homeostasis of gut microbiota during aging. These effects of IAP were also evident in a second model system, Drosophilae melanogaster. IAP appears to preserve intestinal homeostasis in aging by targeting crucial intestinal alterations, including gut barrier dysfunction, dysbiosis, and endotoxemia. Oral IAP supplementation may represent a novel therapy to counteract the chronic inflammatory state leading to frailty and age-related diseases in humans.