PMID: 

Respir Physiol Neurobiol. 2019 Aug ;266:9-17. Epub 2019 Apr 22. PMID: 31022471

Abstract Title: 

Cigarette smoke exposure combined with lipopolysaccharides induced pulmonary fibrosis in mice.

Abstract: 

Cigarette smoke (CS) is a risk factor for pulmonary fibrosis and lipopolysaccharides (LPS) are associated with human occupational lung diseases; however, their combined role in pulmonary fibrosis remains unknown. Therefore, we investigated whether CS combined with LPS induces pulmonary fibrosis in mice. C57BL/6 mice were exposed to CS or normal air for 21 or 35 days, followed by LPS or saline instillation on day 14, 21, and 28. Lung function was tested, and lung tissues were harvested for histological and molecular analyses. Compared to the control, CS and LPS groups, the CS + LPS group showed reduced body weight and survival rate, increased respiratory resistance, decreased lung compliance, marked alveolar structure destruction, and fibrotic lesion formation. Lung tissues showed a considerable increase in IL-6, TNF-α, IL-1β, α-SMA, and TGF-β levels and collagen content. Our results indicate that cigarette smoke exposure followed by LPS in mice induces pulmonary fibrosis with pathophysiology consistent with that of human pulmonary fibrosis.

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PMID: 

Proc Natl Acad Sci U S A. 2019 Oct 7. Epub 2019 Oct 7. PMID: 31591243

Abstract Title: 

Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice.

Abstract: 

Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.

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PMID: 

PLoS One. 2019 ;14(9):e0218143. Epub 2019 Sep 23. PMID: 31545802

Abstract Title: 

Effects from diet-induced gut microbiota dysbiosis and obesity can be ameliorated by fecal microbiota transplantation: A multiomics approach.

Abstract: 

Obesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Hypercaloric diets are tightly related to the obesity etiology and also cause alterations in gut microbiota functionality. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent an accurate strategy to understand its relationship with obesity caused by diet. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function. To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as a complementary obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption. This new approach could be implemented to support the dietary and healthy habits recommended as a first option to maintain the homeostasis of the microbiota.

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PMID: 

Front Behav Neurosci. 2019 ;13:126. Epub 2019 Jun 18. PMID: 31275120

Abstract Title: 

Prophylactic Effects ofon Anxiety and Depression-Like Phenotypes After Chronic Stress: A Role of the Gut Microbiota-Inflammation Axis.

Abstract: 

Stress disturbs the balance of the gut microbiota and stimulates inflammation-to-brain mechanisms. Moreover, stress leads to anxiety and depressive disorders.displays distinct anti-inflammatory effects. However, no report has focused on the anxiolytic and antidepressant effects ofrelated to the gut microbiome and the inflammation on chronic restraint stress (CRS) in mice. We found that pretreatment withincreased the time spent in the center of the open field apparatus, increased the percentage of entries into the open arms of the elevated plus-maze (EPM) and the percentage of time spent in the open arms of the EPM, and decreased the immobility duration in the tail suspension test as well as the forced swimming test (FST). Moreover,increased the sequence proportion ofand reduced the sequence proportion ofin feces. Furthermore,markedly reduced the protein expression of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), p-nuclear factor-kappa B (NF-κB) p65 and Iba1 and elevated brain derived neurotrophic factor (BDNF) expression in the hippocampus. We conclude that the anxiolytic and antidepressant effects ofare related to reducing inflammatory cytokines and rebalancing the gut microbiota.

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PMID: 

Nature. 2019 07 ;571(7766):565-569. Epub 2019 Jul 17. PMID: 31316206

Abstract Title: 

Intestinal infection triggers Parkinson's disease-like symptoms in Pink1mice.

Abstract: 

Parkinson's disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles. An early-onset form of Parkinson's disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes. PINK1 and Parkin (encoded by PRKN) are involved in the clearance of damaged mitochondria in cultured cells, but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo. It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens, which suggests that autoimmune mechanisms participate in the aetiology of Parkinson's disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with L-DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut-brain axis in the disease.

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PMID: 

Curr Opin Pharmacol. 2019 Oct 4 ;48:120-126. Epub 2019 Oct 4. PMID: 31590111

Abstract Title: 

Microbial regulation of microRNA expression in the brain-gut axis.

Abstract: 

The gut microbiome facilitates a consistent transfer of information between the gut and the brain and microRNAs may now represent a key signalling molecule that facilitates this relationship. This review will firstly examine how these small non-coding RNAs influence the gut microbiome, and secondly how the microbiome, when disturbed, may influence miRNA expression in the brain. In addition, we will examine the consequence that microbiome-related changes in miRNA expression have on neurodevelopment, behaviour and cognition. We will also discuss novel data that suggests miRNAs contained in our diet may influence our immune system in a positive manner, offering a further potential pathway for treatment of disorders of the gut-brain axis that are influenced by the microbiome.

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PMID: 

World J Clin Cases. 2019 Sep 6 ;7(17):2597-2604. PMID: 31559298

Abstract Title: 

Fecal microbiota transplantation as an effective initial therapy for pancreatitis complicated with severeinfection: A case report.

Abstract: 

BACKGROUND: Moderately severe acute pancreatitis (MSAP) is a critical form of acute pancreatitis that is related with high morbidity and mortality. Severeinfection (sCDI) is a serious and rare nosocomial diarrheal complication, especially in MSAP patients. Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory and recurrent CDI (rCDI). However, knowledge regarding the initial use of FMT in patients suffering from sCDI is limited.CASE SUMMARY: Here, we report an MSAP patient complicated with sCDI who was treated by FMT as a first-line therapy. The patient was a 51-year-old man who suffered from diarrhea in his course of acute pancreatitis. An enzyme immunoassay was performed to detect toxins, and the result was positive for toxin-producingand toxin B and negative forribotype 027. The colonoscopy revealed pseudomembranous colitis. Due to these findings, sCDI was our primary consideration. Because the patient provided informed consent for FMT treatment, we initially treated the patient by FMT rather than metronidazole. Diarrhea resolved within 5 d after FMT. The patient remained asymptomatic, and the follow-up colonoscopy performed 40 d after discharge showed a complete recovery. Our case is the first reported in China.CONCLUSION: This case explores the possibilities of initially using FMT to treat severe CDI. Moreover, FMT may become a critical component of the treatment for severe CDI in MSAP patients.

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PMID: 

Zhonghua Nei Ke Za Zhi. 2019 Oct 1 ;58(10):782-785. PMID: 31594178

Abstract Title: 

[Fecal microbiota transplantation as a novel therapy for severe psoriasis].

Abstract: 

To explore the therapeutic effect of fecal microbiota transplantation (FMT) for severe psoriasis. A patient, male, 36 years old, diagnosed as severe plaque psoriasis for 10 years and irritable bowel syndrome (IBS) for 15 years, was administrated twice FMT via both upper endoscopy and colonoscopy with a 5-week interval. The following items were used to evaluate responses: body surface area (BSA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), histological examination, intestinal symptoms, adverse reactions and serum level of tumor necrosis factor (TNF)-α. After second FMT treatment for 5 weeks, aforementioned items were improved greatly compared with those before treatment. Moreover, IBS was completely relieved and no adverse reactions were observed during the treatment and follow-up. In conclusion, FMT could be a novel therapy for psoriasis. Further clinical trials are needed to provide solid evidences.

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PMID: 

Gastroenterol Clin North Am. 2019 09 ;48(3):389-405. Epub 2019 Jun 12. PMID: 31383278

Abstract Title: 

Mood and Microbes: Gut to Brain Communication in Depression.

Abstract: 

The gut microbiota, acting via the gut-brain axis, modulates key neurobiological systems that are dysregulated in stress-related disorders. Preclinical studies show that the gut microbiota exerts an influence over neuroimmune and neuroendocrine signaling pathways, in addition to epigenetic modification, neurogenesis, and neurotransmission. In humans, preliminary evidence suggests that the gut microbiota profile is altered in depression. The full impact of microbiota-based treatments, at different neurodevelopmental time points, has yet to be fully explored. The integration of the gut microbiota, as a mediator, in the complex trajectory of depression, may enhance the possibility of personalized precision psychiatry.

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PMID: 

Gastroenterol Clin North Am. 2019 09 ;48(3):407-431. Epub 2019 Jul 2. PMID: 31383279

Abstract Title: 

The Role of the Gut-Brain Axis in Attention-Deficit/Hyperactivity Disorder.

Abstract: 

Genetic and environmental factors play a role in the cause and development of attention-deficit/hyperactivity disorder (ADHD). Recent studies have suggested an important role of the gut-brain axis (GBA) and intestinal microbiota in modulating the risk of ADHD. Here, the authors provide a brief overview of the clinical and biological picture of ADHD and how the GBA could be involved in its cause. They discuss key biological mechanisms involved in the GBA and how these may increase the risk of developing ADHD. Understanding these mechanisms may help to characterize novel treatment options via identification of disease biomarkers.

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