Prospective Cohort Study

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

Colonization resistance — protection from exogenous pathogens by commensal bacteria — can be mediated by direct antagonism and by indirect effects on the host immune response. This Review outlines our current knowledge of immune-mediated colonization resistance against clinically relevant, antibiotic-resistant intestinal pathogens and how insights into commensal bacterial species and their mechanisms might be therapeutically used to restore resistance.

http://www.unizar.es/depfarfi/unidad_fisiologia/Temas%20Teoria/Biotecnologia%20Aplicada/T5_Microbiota%20against%20pathogens.%20Nat%20Rev%20Immunol.%202013.pdf

Microbiota-mediated colonization resistance against intestinal pathogens.

Objective: We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. Methods: An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). Results: Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). Conclusions: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.

Mental Health and Psychosocial Problems of Medical Health Workers during the COVID-19 Epidemic in China.

Should we standardize the 1,700-year-old fecal microbiota transplantation?

Abstact
Background and Aim

The gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel disease. This study aimed to evaluate the safety, feasibility, and efficacy of FMT through mid-gut for refractory Crohn's disease (CD).



Methods

We established standardized laboratory protocol and clinical work flow for FMT. Only refractory CD patients with Harvey–Bradshaw Index (HBI) score ≥ 7 were enrolled for this study. All included patients were treated with single FMT through mid-gut and assessed during follow-up.



Results

Metagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally, 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7% (26/30) and 76.7% (23/30), respectively, which was higher than other assessment points within 15-month follow-up. Patients' body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD.



Conclusion

This is a pilot study with the largest sample of patients with refractory CD who underwent single FMT. The results demonstrated that FMT through mid-gut might be a safe, feasible, and efficient rescue therapy for refractory CD.

Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results.

Fecal microbiota transplantation (FMT) is a promising strategy that involves reconstruction of gut microbiota Recently, it has been considered as a treatment of Crohn's disease (CD) and certain neurological diseases Here, to the best of our knowledge, we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy During the 20 mo of follow-up, FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs Furthermore, this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota

Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report.

Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.

Long noncoding RNA CRNDE promotes colorectal cancer cell proliferation via epigenetically silencing DUSP5/CDKN1A expression.

The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC. Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow-up clinical data was collected for a minimum of 3 months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing. Eight of fourteen (57.1 %) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7 %) received one FMT therapy, one (7.1 %) received two FMTs, and two (14.2 %) received two FMTs plus a scheduled course of steroids. Four (28.6 %) of the 8 patients who responded maintained long-term remission during follow-up (3–18 months). Six patients (42.9 %) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up. Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition. Trial registration: ClinicalTrials.gov, Number NCT01790061

/pdf/step-up-fecal-microbiota-transplantation-strategy-a-pilot-13n9wfl8y9.pdf

Guozhong Ji

Papers

Should we standardize the 1,700-year-old fecal microbiota transplantation?

Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results.

Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report.

Long noncoding RNA CRNDE promotes colorectal cancer cell proliferation via epigenetically silencing DUSP5/CDKN1A expression.

Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis