Microbial invasion of the amniotic cavity is associated with impaired cognitive and motor function at school age in preterm children.

BACKGROUND: Chorioamnionitis is an important cause of preterm delivery. Data on neurodevelopmental outcome in exposed infants are inconsistent due to difficulties in diagnosing intrauterine infection/inflammation and lack of detailed long-term follow-up. We investigate cognitive and motor function in preterm infants at early school age and relate the findings to bacteria in amniotic fluid obtained by amniocentesis (microbial invasion of the amniotic cavity (MIAC)) or placenta findings of histological chorioamnionitis (HCA) or fetal inflammatory response syndrome (FIRS). METHOD: Sixty-six infants with gestational age <34 weeks at birth and without major disabilities were assessed using WISC-III and the Bruininks-Oseretsky Test of Motor Proficiency. Results were corrected for gestational age and sex. RESULTS: Children exposed to MIAC had significantly lower scores for full-scale IQ and verbal IQ compared to the non-MIAC group and the difference in full-scale IQ remained after correction for confounding factors. The MIAC group had also significantly lower motor scores after correction. In contrast, motor function was not affected in infants exposed to HCA or FIRS and differences between groups for cognitive scores were lost after corrections. CONCLUSION: Exposure to bacteria in amniotic fluid is associated with lower motor and cognitive scores in school age preterm infants without major disabilities.

Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD. METHODS: Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice. RESULTS: The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics. CONCLUSIONS: Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.

Gut-brain axis in the executive function of austism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired communication and social interactions, and repetitive behavioural patterns. These patterns are believed to be dysfunctional symptoms in executive processing, which impact other cognitive functions such as attention or cognitive flexibility. In recent years, several studies have shown that certain intestinal bacteria may play a role in shaping cognitive networks encompassing emotional and social domains. A microbiota-gut-brain axis is known to exist, establishing several mechanisms by which microbiota may modulate brain development, function and behaviour, including immune, endocrine and neural pathways. As the aetiology of ASD is largely unknown, some studies have shown that intestinal bacteria may be involved in its pathogenesis. The aim of this review was to focus on the role of the gut-brain axis in ASD and, specifically, on its role in executive functions. First, we summarize the relationship between the gastrointestinal and cognitive symptoms of ASD patients. In addition, we highlight the evidence that supports and emphasizes the involvement of gut microbiota, and the putative underlying mechanisms in this population. Finally, we present evidence from preclinical and clinical studies on the modulation of microbiota and their effects on cognitive symptoms, specifically in relation to executive function. In conclusion, manipulation of microbiota could be a positive intervention to improve ASD symptoms. However, more research evaluating the role of microbiota in the cognitive symptoms ASD is needed.

[Four-year follow-up of a neurosyphilis case presenting psychiatric symptoms]. / Pszichiátriai tünetekkel jelentkezo neuroszifilisz négyéves utánkövetése.

The authors present a case of neurosyphilis associated with predominant psychiatric symptoms. The elderly man was admitted because of confused behavior, maniform state, lack of critical judgement and grandiose delusions. On admission, right central facial nerve paresis, hand tremor and parkinsonism were also found. Acute brain imaging and routine laboratory tests failed to identify a firm etiology of the confusional state. The psychiatric treatment resulted in complete recovery from delirium. Afterwards, maniform psychosis dominated the clinical picture for which antipsychotics were administered. Later, rapid cognitive deterioration and progression of motor symptoms were observed. MRI revealed cortical and hippocampal atrophy and white matter hyperintensities. Lumbar puncture found pleocytosis and elevated cerebrospinal fluid protein levels. Neurosyphilis had been confirmed by serologic tests. The cognitive symptoms improved and the psychiatric symptoms remitted under penicillin treatment. Four years after diagnosis, there is a gradual progression in the cognitive decline. Two additional hospitalizations were necessary due to the relapses of psychiatric symptoms. Orv Hetil. 2018; 159(6): 234-238.

Peripheral aetiopathogenic drivers and mediators of Parkinson's disease and co-morbidities: role of gastrointestinal microbiota.

We seek an aetiopathogenic model for the spectrum of Parkinson's disease (PD), functional bowel disease, depression and cognitive impairment. The adopted concept is that systemic immuno-inflammatory processes mediate neuro-inflammation. The model would be based on phenotype, exposome (including gastrointestinal microbiome), milieu (immuno-inflammatory and metabolome), human genetics and their interactions. It would enable a patient's position, to be understood in terms of drivers, perpetuators and mediators, and a future position, with and without intervention, predicted. Even the cardinal facets of PD may have different drivers: halting one may allow escape down subordinate pathways. Peptic ulceration is prodromal to PD. In our randomised placebo-controlled trial, hypokinesia improved over the year following biopsy-proven Helicobacter pylori eradication and rigidity worsened. This was independent of any (stable, long t½) antiparkinsonian medication. There are pointers to an autoimmune process: for example, surveillance-confirmed hypokinesia effect was indication specific. During surveillance, successive antimicrobial courses, other than for Helicobacter, were associated with cumulative increase in rigidity. Exhibiting laxatives appeared to stem the overall temporal increase, despite antiparkinsonian medication, in rigidity. Thus, intestinal dysbiosis may be a major source of bystander neuronal damage. There are biological gradients of objective measures of PD facets on circulating inflammatory markers and leucocyte subset counts. Moreover, lactulose hydrogen breath test positivity for small-intestinal bacterial overgrowth (present in two thirds of PD patients) is associated with the same subsets: higher natural killer and total CD4+ counts and lower neutrophils. With greater aetiopathogenic understanding, relatively low cost and on-the-shelf medication could have a major impact. A new generation of animal models, based on the gut microbiome, is envisaged.

Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case-control study.

BACKGROUND: Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. METHODS: Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. RESULTS: Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean ± SD: 97.1 ± 4.7 vs. 99.1 ± 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean ± SD -0.29 ± 0.60 vs. 0.09 ± 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean ± SD 11.3 ± 4.2 NB vs. 14.3 ± 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean ± SD -0.15 ± 0.42 NB vs. 0.08 ± 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. CONCLUSION: The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable sequelae of neuroborreliosis. Brain atrophy is not a common consequence of neuroborreliosis.

Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: implications for the gut-liver-brain axis.

UNLABELLED: Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. HYPOTHESIS: Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. METHODS: Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. RESULTS were compared before/after rifaximin. RESULTS: 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.

Neuropsychological profile of children after an episode of neuroborreliosis.

BACKGROUND: In the majority of patients with Lyme neuroborreliosis (LNB), neurological symptoms are transient. The extent of neuropsychological and neuropsychiatric problems in children is not well researched. OBJECTIVES: The study aimed to investigate cognitive functions and behavioral problems in children after LNB. PATIENTS AND METHODS: A total of 20 children between 6 and 16 years of age with an episode of LNB at least 4 month before neuropsychological testing were enrolled in the study and compared with 20 healthy controls. Children with LNB had cranial nerve palsies or meningoencephalitis, immunoglobulin G and immunoglobulin M antibodies for Borrelia burgdorferi in the peripheral blood, pleocytosis in the cerebrospinal fluid (leukocytes > 10 cells/µL) and/or an intrathecal synthesis of antibodies for B. burgdorferi.Neuropsychological tests assessing intellectual skills, memory, and executive functions were used. Two parental questionnaires assessing behavior, psychiatric problems, and executive functions were administered. RESULTS: Intellectual skills, memory, and executive functions of children after an episode of LNB were within the normal range. In the subcategory of working memory, children after an episode of LNB performed worse than controls. The questionnaires did not reveal behavior or psychiatric problems, although there was a tendency that children after an episode of LNB had more physical complaints. CONCLUSION: Neuropsychological deficits resulting from LNB in childhood are rare. Most children had a good cognitive, emotional, and behavioral outcome.

Linkage of gut microbiome with cognition in hepatic encephalopathy.

Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in the setting of intestinal barrier dysfunction. We aimed to link the gut microbiome with cognition and inflammation in HE using a systems biology approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and age-matched controls. Cirrhotics with/without HE underwent cognitive testing, inflammatory cytokines, and endotoxin analysis. Patients with HE were compared with those without HE using a correlation-network analysis. A select group of patients with HE (n = 7) on lactulose underwent stool MTPS before and after lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose, 6 also on rifaximin) and 8 without HE, age 56 ± 6 yr, model for end-stage liver disease score 16 ± 6] and ten controls were included. Fecal microbiota in cirrhotics were significantly different (higher Enterobacteriaceae, Alcaligeneceae, and Fusobacteriaceae and lower Ruminococcaceae and Lachnospiraceae) compared with controls. We found altered flora (higher Veillonellaceae), poor cognition, endotoxemia, and inflammation (IL-6, TNF-α, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae were positively and Ruminococcaceae negatively related to inflammation. Network-analysis comparison showed robust correlations (all P < 1E-5) only in the HE group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose withdrawal did not change the microbiome significantly beyond Fecalibacterium reduction. We concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.

European neuroborreliosis: neuropsychological findings 30 months post-treatment.

BACKGROUND: The aim of this study was to compare neuropsychological (NP) functioning in patients with Lyme neuroborreliosis (LNB) 30months after treatment to matched controls. METHODS: We tested 50 patients with LNB and 50 controls with the trail-making test (TMT), Stroop test, digit symbol test, and California Verbal Learning test (CVLT). A global NP sumscore was calculated to express the number of low scores on 23 NP subtasks. RESULTS: Mean scores were lower amongst LNB-treated patients than amongst controls on tasks assessing attention/executive functions: (Stroop test 4: 77.6 vs. 67.0, P=0.015), response/processing speed (TMT 5: 23.4 vs. 19.2, P=0.004), visual memory (digit symbol recall: 6.6 vs. 7.2, P=0.038), and verbal memory (CVLT list B: 4.68 vs. 5.50, P=0.003). The proportion of patients and controls with NP sumscores within one SD from the mean in the control group (defined as normal) and between one and two SD (defined as deficit) were similar, but more LNB-treated patients than controls had a sumscore more than two SD from the mean (defined as impairment) (8 vs. 1, P=0.014). CONCLUSIONS: As a group, LNB-treated patients scored lower on four NP subtasks assessing processing speed, visual and verbal memory, and executive/attention functions, as compared to matched controls. The distribution of NP dysfunctions indicates that most LNB-treated patients perform comparable to controls, whilst a small subgroup have a debilitating long-term course with cognitive problems.

Cognition, behaviour and academic skills after cognitive rehabilitation in Ugandan children surviving severe malaria: a randomised trial.

BACKGROUND: Infection with severe malaria in African children is associated with not only a high mortality but also a high risk of cognitive deficits. There is evidence that interventions done a few years after the illness are effective but nothing is known about those done immediately after the illness. We designed a study in which children who had suffered from severe malaria three months earlier were enrolled into a cognitive intervention program and assessed for the immediate benefit in cognitive, academic and behavioral outcomes. METHODS: This parallel group randomised study was carried out in Kampala City, Uganda between February 2008 and October 2010. Sixty-one Ugandan children aged 5 to 12 years with severe malaria were assessed for cognition (using the Kaufman Assessment Battery for Children, second edition and the Test of Variables of Attention), academic skills (Wide Range Achievement Test, third edition) and psychopathologic behaviour (Child Behaviour Checklist) three months after an episode of severe malaria. Twenty-eight were randomised to sixteen sessions of computerised cognitive rehabilitation training lasting eight weeks and 33 to a non-treatment group. Post-intervention assessments were done a month after conclusion of the intervention. Analysis of covariance was used to detect any differences between the two groups after post-intervention assessment, adjusting for age, sex, weight for age z score, quality of the home environment, time between admission and post-intervention testing and pre-intervention score. The primary outcome was improvement in attention scores for the intervention group. This trial is registered with Current Controlled Trials, number ISRCTN53183087. RESULTS: Significant intervention effects were observed in the intervention group for learning mean score (SE), [93.89 (4.00) vs 106.38 (4.32), P = 0.04] but for working memory the intervention group performed poorly [27.42 (0.66) vs 25.34 (0.73), P = 0.04]. No effect was observed in the other cognitive outcomes or in any of the academic or behavioural measures. CONCLUSIONS: In this pilot study, our computerised cognitive training program three months after severe malaria had an immediate effect on cognitive outcomes but did not affect academic skills or behaviour. Larger trials with follow-up after a few years are needed to investigate whether the observed benefits are sustained. TRIAL REGISTRATION: ISRCTN: ISRCTN53183087.

Neurocognitive functioning in youth with pediatric autoimmune neuropsychiatric disorders associated with streptococcus.

This study evaluated neurocognitive functioning in 26 youth with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) and primarily obsessive-compulsive disorder (OCD) symptoms. Marked impairment in visuospatial recall memory (as assessed using the Rey-Osterrieth Complex Figure Test) was observed in spite of average to above-average performance on academic and other neurocognitive measures. Group A beta-hemolytic Streptococcus titer elevations were associated with worse performance on tasks of neurocognitive and executive ability (Stroop Color-Word Interference Test), visuospatial memory, and fine motor speed (finger tapping) as well as elevated obsessive-compulsive symptom severity.

Gut dysbiosis in stroke and its implications on Alzheimer's disease-like cognitive dysfunction.

Various neurological disorders, such as stroke and Alzheimer's disease (AD), involve neuroinflammatory responses. The advent of the gut-brain axis enhances our understanding of neurological disease progression and secondary cell death. Gut microbiomes, especially those associated with inflammation, may reflect the dysbiosis of both the brain and the gut, opening the possibility to utilize inflammatory microbiomes as biomarkers and therapeutic targets. The gut-brain axis may serve as a contributing factor to disease pathology and offer innovative approaches in cell-based regenerative medicine for the treatment of neurological diseases. In reviewing the pathogenesis of stroke and AD, we also discuss the effects of gut microbiota on cognitive decline and brain pathology. Although the underlying mechanism of primary cell death from either disease is clearly distinct, both may be linked to gut-microbial dysfunction as a consequential aberration that is unique to each disease. Targeting peripheral cell death pathways that exacerbate disease symptoms, such as those arising from the gut, coupled with conventional central therapeutic approach, may improve stroke and AD outcomes.

The protective effect of Xanthoceras sorbifolia Bunge husks on cognitive disorder based on metabolomics and gut microbiota analysis.

AIM OF THE STUDY: The husks of Xanthoceras sorbifolia Bunge mainly used in north China as folk medicine were reported to have potential protective effect on cognitive impairment. However, the mechanism remains unclear. In order to fully understand the mechanism of the protection, a complementary study of the husks was conducted. MATERIALS AND METHODS: The urinary and fecal metabolomics were used to analyze the potential biomarkers by the liquid chromatography-tandem time of flight mass spectrometry, and the16S rDNA technology was applied to conduct the analysis of microbiota species in the fecal samples of the rats, which is a significant influencing factor for the development of cognitive impairment. RESULTS: In metabolomics study, ten potential metabolic biomarkers, which are hippuric acid, kynurenic acid, creatinine, phenylalanine, xanthurenic acid, phenylacetylglycine, succinyladenosine, cresol sulfate, tryptophan 2-C-mannoside and N4-Acetylcytidine in urine, along with two, including isoleucine and phenylalanine in feces, were preliminarily identified, involving multiple pathways such as tryptophan, purine, kynurenine, and phenylalanine metabolism. The perturbation of these metabolic pathways could be related with insulin resistance, oxidative stress, energy metabolism deficit and neuroinflammation, which were risk factors to cause cognitive impairment. In gut microbiota analysis, the relative abundance of c_Bacteroidia, c_Alphaproteobacteria, f_Prevotellaceae, f_Sphingomonadaceae, f_Burkholderiaceae, g_Prevotellaceae_NK3B31_group and p_Bacteroidetes was significantly changed in the rats with cognitive impairment. Spearman's analysis showed obvious correlation between the metabolites and the microbiota species. In the rats with pretreatment of the husks extract, metabolites maintained a relative normal level, and the husks extract could regulate the gut microbiota, especially f_Prevotellaceae and g_Prevotellaceae_NK3B31_group, indicating the effect of the husks on the metabolic pathways via GMs. Such amino acids as isoleucine and phenylalanine failed to show any significant correlation with the microbiota species, indicating that the husks exhibited the potential protective effect through gut microbiota and other pathways. CONCLUSIONS: The husks extract could improve the intestinal microenvironment, and the stability of intestinal microenvironment was associated with normality of tryptophan, purine, kynurenine and phenylalanine metabolic pathways etc, which probably had an effect on cognitive function. This complementary work suggested that gut microbiotas were potential targets of the husks to exert its effect on cognitive impairment.

Cryptococcal meningitis misdiagnosed as Alzheimer's disease: complete neurological and cognitive recovery with treatment.

A sixty-two year old man, with a background of Alzheimer's disease for the past three years, acutely presented with imbalance, headaches, and dizziness. Examination revealed a profound frontal disinhibited and dysexecutive syndrome and brain imaging notable for leptomeningeal enhancement; laboratory data confirmed cryptococcal meningitis. Four months after treatment, the patient was normal neurologically, cognitively and neuroradiologically. The specific cognitive impairment and neuroradiological findings may be clues to differing dementia etiologies.

Cognitive and motor impairments associated with SIV infection in rhesus monkeys.

Cognitive and motor deficits are now recognized as significant clinical features of infection with the human immunodeficiency virus (HIV). Juvenile rhesus macaques infected with simian immunodeficiency virus (SIV) were found to exhibit cognitive and motor deficits characteristic of HIV infection. Impairment on a motor skill task was the most reliable indicator of infection. Various cognitive impairments were also evident. These deficits were related to SIV infection of the brain but not to inflammatory lesions at a particular locus. The results suggest that the SIV-infected rhesus macaque is a valuable model for understanding the cause of HIV-associated central nervous system dysfunction and for developing a treatment.

Neurobehavioral dysfunction in non-alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits.

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. While it has been suggested to cause nervous impairment, its neurophysiological basis remains unknown. Therefore, the aim of this study is to unravel the effects of NASH, through the interrelationship of liver, gut microbiota, and nervous system, on the brain and human behavior. To this end, 40 Sprague-Dawley rats were divided into a control group that received normal chow and a NASH group that received a high-fat, high-cholesterol diet. Our results show that 14 weeks of the high-fat, high-cholesterol diet induced clinical conditions such as NASH, including steatosis and increased levels of ammonia. Rats in the NASH group also demonstrated evidence of gut dysbiosis and decreased levels of short-chain fatty acids in the gut. This may explain the deficits in cognitive ability observed in the NASH group, including their depressive-like behavior and short-term memory impairment characterized in part by deficits in social recognition and prefrontal cortex-dependent spatial working memory. We also reported the impact of this NASH-like condition on metabolic and functional processes. Brain tissue demonstrated lower levels of metabolic brain activity in the prefrontal cortex, thalamus, hippocampus, amygdala, and mammillary bodies, accompanied by a decrease in dopamine levels in the prefrontal cortex and cerebellum and a decrease in noradrenalin in the striatum. In this article, we emphasize the important role of ammonia and gut-derived bacterial toxins in liver-gut-brain neurodegeneration and discuss the metabolic and functional brain regional deficits and behavioral impairments in NASH.

High-fat diet causes psychiatric disorders in mice by increasing Proteobacteria population.

The excessive intake of a high-fat diet (HFD) leads to obesity, including metabolic syndromes, disturbs gut microbiota composition, causes colitis, and increases the plasma concentration of lipopolysaccharide (LPS). In the present study, we examined the role of gut microbiota in the occurrence of HFD-induced psychiatric disorders in mice. C57BL/6 J male mice fed a HFD for 9 weeks were led to obesity; their memory impairment was assessed by the Y-maze and novel object recognition test, and anxiety-like behaviors by the elevated plus maze. The intake of a HFD suppressed brain-derived neurotrophic factor (BDNF) expression in the hippocampus and increased blood TNF-α and LPS levels. HFD treatment more potently increased NF-κB activation and Iba1+ (microglial) cell populations in the hippocampus. Furthermore, HFD feeding increased TNF-α expression, myeloperoxidase activity, and CD11b+/CD11c+ cell (macrophages and dendritic cells) populations in the colon and altered gut microbiota composition including increases in the Proteobacteria population, and increases in fecal LPS levels. The stool lysates of HFD-treated mice suppressed BDNF expression and CREB phosphorylation in SH-SY5Y cells and increased NF-κB activation in BV-2 microglial cells compared to those of low-fat diet-treated mice while these effects were attenuated by treatment with anti-LPS antibody. These findings suggest that excessive intake of HFD can simultaneously cause obesity and psychiatric disorders by suppressing hippocampal BDNF expression with the disturbance of gut microbiota composition, particularly the increase in Proteobacteria population and LPS production.

Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction.

We detected infection with a Bartonella species (B. henselae or B. vinsonii subsp. berkhoffii) in blood samples from six immunocompetent patients who presented with a chronic neurological or neurocognitive syndrome including seizures, ataxia, memory loss, and/or tremors. Each of these patients had substantial animal contact or recent arthropod exposure as a potential risk factor for Bartonella infection. Additional studies should be performed to clarify the potential role of Bartonella spp. as a cause of chronic neurological and neurocognitive dysfunction.