Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinsons disease, Alzheimers disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).

Background: Studies investigating the changes in short-chain fatty acids (SCFAs) in patients with ulcerative colitis (UC) have yielded inconsistent results. We performed a meta-analysis of studies that investigated the alterations in different SCFAs among UC patients to assess their role in the development of UC. Methods: Three databases were searched for relevant studies published as of April 2021. Results are presented as standardized mean difference (SMD) with 95% confidence interval (95% CI). Results: Eleven studies were included in the meta-analysis. Compared to healthy subjects, UC patients had significantly lower concentrations of total SCFAs (SMD = − 0.88, 95%CI − 1.44, − 0.33; P < 0.001), acetate (SMD = − 0.54, 95% CI − 0.91, − 0.17; P = 0.004), propionate, (SMD = − 0.37, 95% CI − 0.66, − 0.07; P = 0.016), and valerate (SMD = − 0.91, 95% CI − 1.45, − 0.38; P < 0.001). On subgroup analysis based on disease status, patients with active UC had reduced concentrations of acetate (SMD = − 1.83, 95% CI − 3.32, − 0.35; P = 0.015), propionate (SMD = − 2.51, 95% CI − 4.41, − 0.61; P = 0.009), and valerate (SMD = − 0.91, 95% CI − 1.45, − 0.38; P < 0.001), while UC patients in remission had similar concentrations with healthy subjects. Patients with active UC had lower butyrate level (SMD = − 2.09, 95% CI − 3.56, − 0.62; P = 0.005) while UC patients in remission had higher butyrate level (SMD = 0.71, 95% CI 0.33, 1.10; P < 0.001) compared with healthy subjects. Conclusion: UC patients had significantly decreased concentrations of total SCFAs, acetate, propionate, and valerate compared with healthy subjects. In addition, inconsistent changes of certain special SCFAs were observed in UC patients with different disease status.

Background: Paraclostridium bifermentans is the most diverse distributed species of Paraclostridium and can cause fatal human infections under rare conditions. However, its pathogenic mechanisms and adaptation ability behind infections remain unclear. Herein, we reported the complete genome sequence of P. bifermentans HD0315_2 isolated from the feces of a patient with Crohn's disease. Then, we performed genomic analyses to understand its pathogenic mechanisms and adaptation ability.Results: The de novo assembly revealed that the HD0315_2 strain carried a circular chromosome of 3.27 Mb and six circular plasmids (19.41 to 139.50 kb). The phylogenomic analysis assigned the HD0315_2 strain as P. bifermentans and reclassified some previously non-P. bifermentans strains into this clade. The general genomic features showed that this species harbored a flexible genomic pool characterized by variable genome length and multiple plasmids. Then, the HD0315_2 strain was predicted as a human pathogen with high probability, and Listeria LIPI-1 virulence proteins were identified on its genome. Besides, abundant antibiotics/metal/stress resistant genes, such as asrABCH, cat, mccF, macB, entS, albA, bcrA, and tetB, were carried by either the genome or the plasmids. Furthermore, we proposed that transposase-directed horizontal gene transfer was responsible for the distribution of multiple copies of the hin gene in the plasmids.Conclusion: The flexible genomic pool of P. bifermentans encodes abundant functions for antimicrobial or oxidative stress resistance, helping it successfully inhabit and adapt to diverse environments. Moreover, P. bifermentans HD0315_2 might infect hosts via a Listeria LIPI-1-like cycle, with the help of a plasmid expressing the Hin DNA invertase to evade host immune responses.

Background. Fecal microbiota transplantation (FMT) has been found to be effective in irritable bowel syndrome with predominant diarrhea (IBS‐D). We conducted this study to determine the impact of a low FODMAP diet (LFD) on the gut microbiota and the efficacy of FMT in the treatment of IBS‐D. Methods. A retrospective analysis of a single‐arm open‐label prospective study was conducted to investigate the impact of FMT alone (n = 40) and FMT+LFD (n = 40) in refractory IBS‐D. The IBS‐quality of life (QOL), IBS‐severity scoring system (SSS), gastrointestinal symptom rating scale (GSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD) were used to evaluate the efficacy, and partial 16S rDNA amplicon sequencing was used to profile the microbiota. Results. The response rates were higher in the FMT+LFD group than in the FMT group (1 mo, 3 mo, 6 mo: 70.0% vs. 55.0%, 67.5% vs. 57.5%, 62.5% vs. 27.5%, respectively). The FMT+LFD group showed significantly better improvement in IBS‐QOL at 1, 3, and 6 months; IBS‐SSS at 6 months; and GSRS at 1 month compared to FMT alone. Changes in HAMA and HAMD were similar in the two groups. The LFD significantly upregulated the FMT‐induced microbial diversity (OTUs: 666 vs. 574, Adonis: P = 0.02) and significantly strengthened the upregulation of Bacteroides, Alistipes, and Ruminococcaceae_UCG-002 and the downregulation of Bifidobacterium. Conclusion. An LFD enhanced the efficacy of FMT, increased the gut microbial diversity after FMT, and strengthened the inhibitory effect of FMT on conditional pathogens.

Background and Aim. The enteric microbiota is able to cross‐talk with factors involved in the blockade of programmed cell death protein 1 (PD‐1) and also plays an important role in the predisposition and onset of inflammatory bowel disease (IBD). The current study used a mouse model of experimental colitis to determine the pathogenic connection between PD‐1 inhibition, gut microbiota, and IBD. Methods. Colitis was induced in mice using 2,4,6‐trinitrobenzene‐sulfonic acid (TNBS), and mice were subsequently treated with either a PD‐1 inhibitor or 5‐amino‐salicylic acid (ASA) as a positive control. Body weight, disease activity index (DAI), colon length, and tissue damage were evaluated, and the enteric microbiota was profiled using high‐throughput 16S rRNA sequencing of fecal samples from the experimental mice. Results. TNBS caused mice to experience IBD‐like symptoms, which were attenuated by the PD‐1 inhibitor, as indicated by a decrease in DAI scores (p = 0.0002). Furthermore, in this mouse model of IBD, PD‐1 inhibition improved the alpha diversity as well as restored the beta diversity of the enteric microbiome. It also significantly enriched the abundance of short‐chain fatty acid‐ (SCFA‐) producing bacteria of the Firmicutes (p < 0.05) and Bacteroidetes (p < 0.05) phyla but depopulated Proteobacteria (p < 0.05). Conclusion. PD‐1 inhibition can partly mitigate TNBS‐induced colitis and restore the enteric microbiota by enriching the abundance of SCFA‐producing bacteria.

Clinical neutropenia, a blood disorder marked by faulty neutrophil production, resists effective treatment due to developmental bottlenecks in granulopoiesis. While the current therapy, such as granulocyte colony‐stimulating factor (G‐CSF), boosts neutrophil counts, its late‐stage action mobilizes dysfunctional cells, underscoring the need for early‐lineage therapeutic interventions. Leveraging zebrafish models, we found that transcriptional enhanced associate domain 1a (TEAD1a) initiates transcriptional priming to govern neutrophil lineage specification preceding hematopoietic stem cell formation. Genetic ablation of TEAD1a or disruption of its interaction with Yes‐associated protein 1 (YAP1) induces profound neutropenia. Mechanistic interrogation reveals that TEAD1a/YAP1 complexes potentiate Notch1‐mediated signaling to activate a Spi1/Cebpα transcriptional cascade during myeloid progenitor specification. This study uncovers a novel developmental regulatory window for myeloid lineage commitment and demonstrates the evolutionarily conserved role of TEAD1a‐mediated transcriptional priming in orchestrating neutrophil development. The discovery of this ultra‐early regulatory node provides a molecularly defined target for generating developmentally competent neutrophils, offering an innovative therapeutic strategy for refractory neutropenia.