Orally Administered Antibiotics Vancomycin and Ampicillin Cause Cognitive Impairment With Gut Dysbiosis in Mice With Transient Global Forebrain Ischemia

Gut microbiota is closely associated with the occurrence of neuropsychiatric disorders. Antibiotics are frequently used to prevent pathogen infection in patients with brain ischemia. To understand the impact of prophylactic antibiotic treatment for patients with brain ischemia, we examined the effects of orally administered vancomycin and ampicillin on cognitive function and gut microbiota composition in mice with transient global forebrain ischemia (tIsc). tIsc operation and orally gavaged vancomycin mildly and moderately caused cognitive impairment, respectively. However, the exposure of mice with tIsc to vancomycin or ampicillin severely impaired cognitive function in the Y-maze, novel object recognition, and Banes maze tasks. Furthermore, their treatments induced NF-κB activation as well as active microglia (NF-κB+/Iba1+ and LPS+/Iba1+ cells) and apoptotic (caspase 3+/NeuN+) cell population in the hippocampus, whereas the brain-derived neurotrophic factor (BDNF)+/NeuN+ cell populations decreased. These treatments also caused colitis and gut dysbiosis. They increased the population of Proteobacteria including Enterobacter xiangfangenesis. Orally delivered fecal transplantation of vancomycin-treated mice with or without tIsc and oral gavage of Enterobacter xiangfangenesis also significantly deteriorated the cognitive impairment and colitis in transplanted mice with tIsc. These findings suggest that oral administration of antibiotics can deteriorate cognitive impairment with gut dysbiosis in patients with brain ischemia.

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The Oxford Handbook of Adult Cognitive Disorders

10.1093/oxfordhb/9780190664121.001.0001 ◽

2019 ◽

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Neurodevelopmental Disorders ◽

Brain Aging ◽

Cognitive Disorders ◽

Diverse Range ◽

Medical Specialties ◽

Psychiatric Illnesses ◽

Medical Disorders ◽

The Impact

The prevalence of cognitive impairment caused by neurodegenerative diseases and other neurologic disorders associated with aging is expected to rise dramatically between now and year 2050, when the population of Americans aged 65 or older will nearly double. Cognitive impairment also commonly occurs in other neurologic conditions, as well as in non-neurologic medical disorders (and their treatments), idiopathic psychiatric illnesses, and adult neurodevelopmental disorders. Cognitive impairment can thus infiltrate all aspects of healthcare, making it necessary for clinicians and clinical researchers to have an integrated knowledge of the spectrum of adult cognitive disorders. The Oxford Handbook of Adult Cognitive Disorders is meant to serve as an up-to-date, scholarly, and comprehensive volume covering most diseases, conditions, and injuries resulting in impairments in cognitive function in adults. Topics covered include normal cognitive and brain aging, the impact of medical disorders (e.g., cardiovascular, liver, pulmonary) and psychiatric illnesses (e.g., depression and bipolar disorder) on cognitive function, adult neurodevelopmental disorders (e.g., Down Syndrome, Attention Deficit/Hyperactivity Disorder), as well as the various neurological conditions (e.g., Alzheimer’s disease, chronic traumatic encephalopathy, concussion). A section of the Handbook is also dedicated to unique perspectives and special considerations for the clinicians and clinical researchers, covering topics such as cognitive reserve, genetics, diversity, and neuroethics. The target audience of this Handbook includes: (1) clinicians, particularly psychologists, neuropsychologists, neurologists (including behavioral and cognitive neurologists), geriatricians, and psychiatrists (including neuropsychiatrists), who provide clinical care and management for adults with a diverse range of cognitive disorders; (2) clinical researchers who investigate cognitive outcomes and functioning in adult populations; and (3) graduate level students and post-doctoral trainees studying psychology, clinical neuroscience, and various medical specialties.

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Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice

Microbiome ◽

10.1186/s40168-021-01088-9 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Hong Zheng ◽

Pengtao Xu ◽

Qiaoying Jiang ◽

Qingqing Xu ◽

Yafei Zheng ◽

...

Keyword(s):

Cognitive Impairment ◽

Gut Microbiota ◽

Cognitive Functions ◽

Neural Mechanism ◽

Fecal Microbiota ◽

Protective Role ◽

Fecal Microbiota Transplant ◽

Memory Impairments ◽

The Impact

Abstract Background Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism. Results We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy. Conclusions Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.

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Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

Microorganisms ◽

10.3390/microorganisms7100456 ◽

2019 ◽

Vol 7 (10) ◽

pp. 456 ◽

Cited By ~ 9

Author(s):

Kaliyan Barathikannan ◽

Ramachandran Chelliah ◽

Momna Rubab ◽

Eric Banan-Mwine Daliri ◽

Fazle Elahi ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Molecular Mechanisms ◽

Short Chain Fatty Acids ◽

Genetic Profile ◽

Fecal Transplantation ◽

Intestinal Microbes ◽

Prevalence Of Obesity ◽

Future Direction ◽

The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

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Prospective Associations of Erythrocyte Composition and Dietary Intake of n-3 and n-6 PUFA with Measures of Cognitive Function

Nutrients ◽

10.3390/nu10091253 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1253 ◽

Cited By ~ 5

Author(s):

Sherman Bigornia ◽

Tammy Scott ◽

William Harris ◽

Katherine Tucker

Keyword(s):

Cognitive Impairment ◽

Executive Function ◽

Cognitive Function ◽

Dietary Intake ◽

Puerto Rican ◽

Cognitive Domain ◽

Health Study ◽

Individual Species ◽

Dietary Pufa ◽

The Impact

Polyunsaturated fatty acid (PUFA) consumption is recommended as part of a healthy diet, but evidence of the impact of individual species and biological concentrations on cognitive function is limited. We examined prospective associations of PUFA erythrocyte composition and dietary intake with measures of cognitive function among participants of the Boston Puerto Rican Health Study (aged 57 years). Erythrocyte and dietary PUFA composition were ascertained at baseline and associated with 2-year scores on the Mini-Mental State Exam (MMSE) (n = 1032) and cognitive domain patterns derived from a battery of tests (n = 865), as well as with incidence of cognitive impairment. Erythrocyte and dietary n-3 PUFA were not significantly associated with MMSE score. However, total erythrocyte and dietary n-3 very-long-chain fatty acids (VLCFA), and intake of individual species, were associated with better executive function (P-trend < 0.05, for all). There was evidence that greater erythrocyte n-6 eicosadienoic acid concentration was associated with lower MMSE and executive function scores (P-trend = 0.02). Only erythrocyte arachidonic acid (ARA) concentration predicted cognitive impairment (Odds Ratio = 1.26; P = 0.01). Among Puerto Rican adults, we found that n-3 VLCFA consumption may beneficially impact executive function. Further, these findings provide some evidence that n-6 metabolism favoring greater ARA tissue incorporation, but not necessarily dietary intake, could increase the risk of cognitive impairment.

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2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2257 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S896-S896

Author(s):

Benoit Levast ◽

Cécile Batailler ◽

Cécile Pouderoux ◽

Lilia Boucihna ◽

Sébastien Lustig ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Joint Infection ◽

Surrogate Marker ◽

Generation Cephalosporin ◽

Fecal Microbiota ◽

Metagenomic Sequencing ◽

Gut Dysbiosis ◽

Prosthetic Joint ◽

The Impact

Abstract Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

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Exercise-Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/1697070 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Zhao Jin ◽

Zongze Zhang ◽

Jianjuan Ke ◽

Yanlin Wang ◽

Huisheng Wu

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Cerebral Ischemia ◽

Enzyme Linked Immunosorbent Assay ◽

Ros Generation ◽

Mice Model ◽

Stroke Patients ◽

Neuroprotective Effects ◽

Protein Expressions ◽

The Impact

Irisin, which can be released in the hippocampus after physical exercise, is demonstrated to have beneficial effects on neurovascular diseases. This study investigated the impact of exercise linked-irisin on mortality and cognition in a mice model of cerebral ischemia and further explored its underlying mechanism. The cerebrospinal concentrations of irisin and klotho from ischemic stroke patients were measured with an enzyme-linked immunosorbent assay (ELISA). The cognitive function of mice was evaluated by a series of behavioural experiments. The expressions of klotho, MnSOD, and FOXO3a in the hippocampus of mice were detected by Western blot. Superoxide production in the brain tissue of mice was evaluated with the dihydroethidium (DHE) dying. The results demonstrated that stroke patients showed a positive correlation between their CSF irisin concentration and klotho concentration. In addition, when mice subjected to cerebral ischemia, their cognitive function was impaired, the protein expressions of klotho, MnSOD, and FOXO3a downregulated, and the production of reactive oxygen species (ROS) increased compared with the sham group. After pretreatment with exogenous irisin, improved cognitive impairment, upregulated protein expressions of klotho, MnSOD, and FOXO3a, and reduced ROS generation were observed in mice with MCAO. However, the neuroprotective effects of irisin compromised with the evidence of severe cognitive impairment, decreased protein expressions of MnSOD and FOXO3a, and increased ROS production in klotho knockout mice. Thus, our results indicated that exercise-linked irisin could prevent mortality and improve cognitive impairment after cerebral ischemia by regulating klotho expression.

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Cognitive Enhancement Therapy in Schizophrenia

Jurnal Psikiatri Surabaya ◽

10.20473/jps.v9i1.17515 ◽

2020 ◽

Vol 9 (1) ◽

pp. 7

Author(s):

Zain Budi Syulthoni ◽

I Gusti Ngurah Gunadi

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Social Cognitive ◽

Cognitive Enhancement ◽

Late Onset ◽

Rehabilitation Program ◽

The Impact ◽

Additional Therapy ◽

The Brain ◽

Back To Work

Schizophrenia is a chronic, severe, and debilitate mental disorder that causing disability. Factors that causing disability is cognitive impairment. Cognitive impairment caused by disturbance in neurodevelopmental process of the brain that related to Dopaminergic, GABA-ergic, and Acethylcholinergic pathway. Cognitive Enhancement Therapy is additional therapy to recovery the cognitive function. CET facilitated repairmenin socio and non-socio cognitive function, encourage patient behaviour related social condition, develop patient understanding of schizophrenia and the impact on cognitive impair- ment, and rehabilitation program that characterised of an experiential and exercise to repair the non-social cognitive function (attention, memmory, and problem solving). CET shows improvement in early or late onset of schizophrenia. Pa- tients who got CET can back to work. Now, CET is used for early intervention in cognitive impairment in Schizophrenia. CET was also developed in patients with Schizoaffective, Schizophrenia comorbid with drug abuse, and patientswith au- tism. Hopefully, the improvement onquality of life patient with schizophrenia can achieve with combination pharmacother- apy and Cognitive Enhancement Therapy.

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Cognitive Functions under Anti-HER2 Targeted Therapy in Cancer Patients: A Scoping Review

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200729153009 ◽

2020 ◽

Vol 20 ◽

Author(s):

Javier García-Sánchez ◽

María D. Torregrosa ◽

Omar Cauli

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Cancer Patients ◽

Cognitive Functions ◽

Uterine Cancer ◽

Cochrane Library ◽

Acute Administration ◽

Breast Cancer Patients ◽

Her 2 ◽

The Impact

Background and Objective: Pharmacological therapy targeting the HER2 protein is one of the major breakthroughs in the treatment of cancer patients overexpressing HER2 who have increased survival rates. Despite improved survival, it is important to determine the less frequent adverse effects in order to tailor treatments more personalized to the patients’ features. The possible impact of cancer treatments on cognitive functions is huge, and the effects of anti-HER 2 therapies on this issue have not been reviewed and are the objective of this study. Results: Analysis of PubMed, Scopus, Cochrane library and Web of Science databases revealed six studies performed in breast and serous uterine cancer patients analyzing cognitive function under chemotherapy regimens including anti-HER2 drugs. Four of these studies reported small to significant worsening of cognitive function following chemotherapy regimens containing trastuzumab (the most widely used anti-HER2 drug). In neoadyuvant settings, and in breast cancer patients, treatment with the new anti-HER-2 drug trastuzumab emtansine seems to induce less cognitive impairment than therapeutic regimens containing chemotherapy and trastuzumab. Acute administration of trastuzumab induced cognitive impairment in gastric cancer mice models, confirming its ability to alter cognitive function in patients,. Conclusions: More studies analyzing the impact of anti-HER2 therapy on cognitive function are necessary at preclinical and clinical levels in order to personalize pharmacological treatment and offers cancer patients a better quality of life.

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Insulin and cognitive function in humans: experimental data and therapeutic considerations

Biochemical Society Transactions ◽

10.1042/bst0331037 ◽

2005 ◽

Vol 33 (5) ◽

pp. 1037-1040 ◽

Cited By ~ 23

Author(s):

M.W.J. Strachan

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Memory Function ◽

Experimental Studies ◽

Epidemiological Studies ◽

Therapeutic Benefit ◽

Systemic Absorption ◽

Intravenous Insulin ◽

People With Dementia ◽

The Impact

Data from experimental studies in animals and from epidemiological studies in humans suggest a link between insulin and cognitive performance. Do these results translate into clinical and therapeutic benefit for people with cognitive impairment? Insulin injected peripherally can readily cross the blood–brain barrier. Intravenous insulin can improve aspects of cognitive function in healthy adults and in individuals with Alzheimer's dementia. Moreover, intravenous insulin increases concentrations of a long form of β-amyloid protein, Aβ42. One potential confounding factor with these data, however, is the need for co-administration of glucose with the insulin to maintain euglycaemia as glucose itself can facilitate memory function. Administration of insulin via the intranasal route is scientifically (and therapeutically) more attractive because the insulin goes directly to the cerebrospinal fluid, with minimal systemic absorption; this obviates the need for a glucose infusion. Intranasal insulin may improve some aspects of memory in healthy individuals, but has yet to be studied in people with cognitive impairment. TZDs (thiazolidinediones) reduce peripheral insulin concentrations by enhancing insulin sensitivity. In adults with Type II (non-insulin-dependent) diabetes, TZD therapy improves memory function, but so does sulphonylurea therapy (which elevates peripheral insulin concentrations). Improved memory is linked to lower blood glucose concentrations, rather than altered insulin levels. However, major trials are currently under way examining the impact of TZDs in people with dementia.

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