Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance

Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health‐promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviours such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioural and biological responses to stress later in life. Juvenile, male F344 rats were fed diets containing either GOS and PDX alone, LAC alone, or GOS, PDX and LAC. All diets altered gut bacteria, while diets containing GOS and PDX increased Lactobacillus spp. After 4 weeks, rats were exposed to inescapable stress, and either immediately killed for blood and tissues, or assessed for learned helplessness 24 h later. Diets did not attenuate stress effects on spleen weight, corticosterone and blood glucose; however, all diets differentially attenuated stress‐induced learned helplessness. Notably, in situ hybridization revealed that all diets reduced stress‐evoked cfos mRNA in the dorsal raphe nucleus (DRN), a structure important for learned helplessness behaviours. In addition, GOS, PDX and LAC diet attenuated stress‐evoked decreases in mRNA for the 5‐HT_1A autoreceptor in the DRN and increased basal BDNF mRNA within the prefrontal cortex. These data suggest early life diets containing prebiotics and/or LAC promote behavioural stress resistance and uniquely modulate gene expression in corresponding circuits.     

研究植物乳杆菌对肠道细菌易位的抑制作用

目的 研究植物乳杆菌对肠道细菌易位的抑制作用.方法 将SD大鼠随机分为4组,即假手术对照组,乳杆菌L2灌胃组,缺血再灌注(Ischemia/Reperfusion,I/R)组,乳杆菌预处理+缺血再灌注组.观察各组动物肠黏膜形态病理学变化、肠道菌群变化、细菌易位、血浆细胞因子的水平.结果 与假手术对照组相比,缺血再灌注组大鼠肠黏膜有明显病理损伤改变,肠黏膜出现坏死、脱落.肠道内厌氧菌数量显著下降,肠杆菌数量也有所下降.在肝、脾、肾及肠系膜淋巴结中有细菌存在,其易位率达87.5％ (P＜0.01).乳杆菌灌胃组大鼠各项指标无显著变化,乳杆菌预处理+I/R组其变化程度较之缺血再灌注组显著减弱.结论 植物乳杆菌L2能够抑制肠道缺血再灌注损伤引起的细菌易位,减弱其对肠黏膜屏障的损伤.     

Resting-state EEG gamma power and theta–gamma coupling enhancement following high-frequency left dorsolateral prefrontal rTMS in patients with depression

Objective

We aimed to investigate neuromodulatory effects of high-frequency left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) on resting-state electroencephalography (EEG) and their clinical and cognitive correlates in patients with depression.

Epileptogenic high-frequency oscillations skip the motor area in children with multilobar drug-resistant epilepsy

Objective

Subtotal hemispherectomy involves the resection of multiple lobes in children with drug-resistant epilepsy, skipping the motor area (MA). We determined epileptogenicity using the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI), demonstrating strength of coupling between HFO and slow wave. We hypothesized that epileptogenicity increased over the multiple lobes but skipped the MA.

Protease‐activated receptor 2 contributes to Toxoplasma gondii‐mediated gut inflammation

Toxoplasma gondii is a widespread intracellular parasite, which naturally enters the organism via the oral route and crosses the intestinal barrier to disseminate. In addition to neuronal and ocular pathologies, this pathogen also causes gut inflammation in a number of animals. This infection‐triggered inflammation has been extensively studied in the C57BL/6 mice, highlighting the importance of the immune cells and their mediators in the development of gut pathology. However, despite their importance in inflammation, the role of protease‐activated receptors (PAR) was never reported in the context of T.gondii‐mediated small intestine inflammation. Using genetically modified mice, we show that PAR₂ plays a pathogenic role in the development of gut inflammatory lesions. We find that PAR₂ controls the innate inflammatory mediators IL‐6, KC/CXCL1, PGE₂ as well as neutrophil infiltration in T. gondii‐triggered gut damage. These results bring new knowledge on the mechanisms operating in the gut in response to T. gondii infection.     

Clinical Benefit of Ablating Localized Sources for Human Atrial Fibrillation: The Indiana University FIRM Registry

Background

Mounting evidence shows that localized sources maintain atrial fibrillation (AF). However, it is unclear in unselected “real-world” patients if sources drive persistent atrial fibrillation (PeAF), long-standing persistent atrial fibrillation (LPeAF), or paroxysmal atrial fibrillation (PAF); if right atrial sites are important; and what the long-term success of source ablation is.

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.     

Gastrointestinal dysbiosis and the use of fecal microbial transplantation in Clostridium difficile infection

The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections (CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation (FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities.     

Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.