Different care mode alter composition and function of gut microbiota in cerebral palsy children.

Introduction: Specialized care is essential for the recovery of children with cerebral palsy (CP). This study investigates how different care modes impact the gut microbiota. Methods: Fecal samples from 32 children were collected, among whom those cared for by family (n = 21) were selected as the observation group, and those cared for by children's welfare institutions (n = 11) were selected as the control group (registration number of LGFYYXLL-024). The gut microbiota profiles were analyzed. Results: There was no significant difference in the α-diversity of the gut microbiota and the abundance at the phylum level. However, at the genus level, the observation group showed a significant increase in the abundance of butyrate-producing bacteria Bacteroides and Lachnospiracea incertae sedis (P < 0.05), and a significant decrease in the abundance of opportunistic pathogens Prevotella, Clostridium cluster IV, Oscillibacter, and Fusobacterium (P < 0.05). Additionally, lipid metabolism, carbohydrate metabolism, transcription, cellular processes and signaling, and membrane transport were significantly upregulated in the observation group. Lipid metabolism was positively correlated with Bacteroides and Lachnospiracea incertae sedis, indicating a positive impact of the family-centered care mode on bacterial metabolism processes. Discussion: This study highlights that the family-centered care mode had a positive impact on the composition and function of the gut microbiota. The study provides valuable insights into the relationship between care mode and gut microbiota, which can inspire the development of interventions for cerebral palsy.

From whole genomes to probiotic candidates: A study of potential lactobacilli strains selection for vaginitis treatment.

Vaginitis, characterized by pathogenic invasion and a deficiency in beneficial lactobacilli, has recognized lactobacilli supplementation as a novel therapeutic strategy. However, due to individual differences in vaginal microbiota, identifying universally effective Lactobacillus strains is challenging. Traditional methodologies for probiotic selection, which heavily depend on extensive in vitro experiments, are both time-intensive and laborious. The aim of this study was to pinpoint possible vaginal probiotic candidates based on whole-genome screening. We sequenced the genomes of 98 previously isolated Lactobacillus strains, annotating their genes involved in probiotic metabolite biosynthesis, adherence, acid/bile tolerance, and antibiotic resistance. A scoring system was used to assess the strains based on their genomic profiles. The highest-scoring strains underwent further in vitro evaluation. Consequently, two strains, Lactobacillus crispatus LG55-27 and Lactobacillus gasseri TM13-16, displayed an outstanding ability to produce d-lactate and adhere to human vaginal epithelial cells. They also showed higher antimicrobial activity against Gardnerella vaginalis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa compared to reference Lactobacillus strains. Their resilience to acid and bile environments highlights the potential for oral supplementation. Oral and vaginal administration of these two strains were tested in a bacterial vaginosis (BV) rat model at various doses. Results indicated that combined vaginal administration of these strains at 1 × 106 CFU/day significantly mitigated BV in rats. This research offers a probiotic dosage guideline for vaginitis therapy, underscoring an efficient screening process for probiotics using genome sequencing, in vitro testing, and in vivo BV model experimentation.

Orally administrated Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 can restore the vaginal health of patients recovering from bacterial vaginosis.

Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.

Evaluation of the Impact of BaP Exposure on the Gut Microbiota and Allergic Responses in an OVA-Sensitized Mouse Model.

BACKGROUND: Exposure to environmental pollutants, including benzo[a]pyrene (BaP), has been implicated in allergic diseases and intestinal microbiota homeostasis, but the environment-microbiota-immunity triangular relationship and to what extent BaP-induced remodeling of the gut microbiota contributes to intestinal allergic inflammation remain to be established. OBJECTIVES: We investigated the impact of BaP on intestinal allergic inflammation and examined the relationship between this effect and gut microbiota dysbiosis. We explored the potential ability of intestinal bacteria to degrade BaP and alleviate cytotoxicity as a detoxification strategy to counteract the effects of BaP exposure. METHODS: We combined microbiome shotgun metagenomics with animal histological and intestinal allergic inflammatory responses to assess the effects of BaP (50µg/mouse per day) in a 23-d toxicity test in antigen-induced allergic female mice. In addition, genome annotation, quantitative analysis of BaP, and in vitro cytotoxicity-tests using CaCo-2 cells were conducted to infer the role of intestinal bacteria in BaP detoxification. RESULTS: BaP exposure impacted the taxonomic composition and the functional potential of the gut microbiota and aggravated antigen-induced intestinal allergic inflammatory responses. The level of inflammatory cytokines correlated with the abundance of specific bacterial taxa, including Lachnospiraceae bacterium 28-4 and Alistipes inops. We identified 614 bacteria harboring genes implicated in the degradation of BaP, and 4 of these bacterial strains were shown to significantly reduce the cytotoxicity of BaP to CaCo-2 cells in vitro. DISCUSSION: Using allergic female mice as a model, we investigated the relationship between BaP, microbiota, and host immune reactions, highlighting the role of gut bacteria in BaP-aggravated allergic reactions. Our findings offer novel insight toward establishing the causal relationship between BaP exposure and the occurrence of allergic disorders. Identifying gut bacteria that degrade BaP may provide new strategies for ameliorating BaP cytotoxicity. https://doi.org/10.1289/EHP11874.

Corrigendum: Dietary fiber and probiotics based on gut microbiota targeting for functional constipation in children with cerebral palsy.

[This corrects the article DOI: 10.3389/fped.2022.1001789.].

Dietary fiber and probiotics based on gut microbiota targeting for functional constipation in children with cerebral palsy.

Gastrointestinal (GI) disorders are very common among children with cerebral palsy. Gut microbiota has been confirmed to maintain normal GI physiological function and further contributed to cerebral palsy through the gut-brain axis. Our study was to investigate the effect of dietary fiber combined with probiotics on functional constipated children with cerebral palsy. In total, 35 patient children were enrolled and divided into general diet group (n = 14) and liquid diet group (n = 21). All the participants received Compound Dietary Fiber (CDF) for 1 month and lactic acid-producing and butyric acid-producing probiotics for 6 months. After a 1-month intervention, the frequency of spontaneous and manual defecation, and Bristol score were all significantly improved (P < 0.001). The α-diversity of the gut microbiota was significantly increased after a 1-month intervention (P < 0.05), with a higher abundance of butyric acid-producing bacteria and a lower abundance of opportunistic pathogens (P < 0.05, FDR < 0.05). However, the impersistent effect of the 6-month intervention suggested the insufficient impact of intaking probiotics alone and the short duration of CDF intervention. Moreover, although the intervention had affected the constipation symptoms equally in cerebral palsy children with a general diet and liquid diet, the general diet group showed a greater and more durable change in gut microbiota and clinical phenotypes after intervention than the liquid diet group, which indicated that longer intervention time should be considered for liquid diet children. This study not only illustrated that supplementation of dietary fiber combined with probiotics can improve functional constipation in children with cerebral palsy, but also provides guidance for optimal intervention strategy for future studies, which will further benefit cerebral palsy children. Clinical trial registration: http://www.chictr.org.cn/showproj.aspx?proj=46902, identifier: ChiCTR1900028257.

Phenotypic and functional alteration of CD45+ immune cells in the decidua of preeclampsia patients analyzed by mass cytometry (CyTOF).

Preeclampsia (PE) is a severe placenta-related pregnancy disease that has been associated with maternal systemic inflammation and immune system disorders. However, the distribution and functional changes in immune cells of the maternal-placental interface have not been well characterized. Herein, cytometry by time-of-flight mass spectrometry (CyTOF) was used to investigate the immune atlas at the decidua, which was obtained from four PE patients and four healthy controls. Six superclusters were identified, namely, T cells, B cells, natural killer (NK) cells, monocytes, granulocytes, and others. B cells were significantly decreased in the PE group, among which the reduction in CD27+CD38+ regulatory B cell (Breg)-like cells may stimulate immune activation in PE. The significantly increased migration of B cells could be linked to the significantly overexpressed chemokine C-X-C receptor 5 (CXCR5) in the PE group, which may result in the production of excessive autoantibodies and the pathogenesis of PE. A subset of T cells, CD11c+CD8+ T cells, was significantly decreased in PE and might lead to sustained immune activation in PE patients. NK cells were ultimately separated into four subsets. The significant reduction in a novel subset of NK cells (CD56-CD49a-CD38+) in PE might have led to the failure to suppress inflammation at the maternal-fetal interface during PE progression. Moreover, the expression levels of functional markers were significantly altered in the PE group, which also inferred that shifts in the decidual immune state contributed to the development of PE and might serve as potential treatment targets. This is a worthy attempt to elaborate the differences in the phenotype and function of CD45+ immune cells in the decidua between PE and healthy pregnancies by CyTOF, which contributes to understand the pathogenesis of PE, and the altered cell subsets and markers may inspire the immune modulatory therapy for PE.

Probiotic Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 as an Adjunctive Treatment for Bacterial Vaginosis Do Not Increase the Cure Rate in a Chinese Cohort: A Prospective, Parallel-Group, Randomized, Controlled Study.

The purpose of this study was to evaluate the effectiveness of metronidazole and oral probiotics adjunct to metronidazole in the treatment of bacterial vaginosis (BV). One hundred and twenty-six Chinese women with BV were enrolled in this parallel, controlled trial, and were randomly assigned into two study arms: the metronidazole group, which was prescribed metronidazole vaginal suppositories for 7 days, and the adjunctive probiotic group, which received Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 orally for 30 days as an adjunct to metronidazole. Clinical symptoms and Nugent scores at the initial visit, 30 days and 90 days were compared. There was no significant difference of the 30-day total cure rate between the adjunctive probiotic group (57.69%) and the metronidazole group (59.57%), with an odds ratio (OR) of 0.97 (95% confidence interval (CI), 0.70 to 1.35, p-value = 0.04), or of the 90-day total cure rate (36.54% vs. 48.94%, OR, 0.75; 95% CI, 0.47 to 1.19; p-value = 0.213). Also, no significant difference of the vaginal and faecal microbial diversity and structure between the two groups at 0, 30 or 90 days were shown based on 16S rRNA sequences. The probiotic species were rarely detected in either the vaginal microbiota or the faecal microbiota after administration which may revealed the cause of noneffective of oral probiotics. No serious adverse effects were reported in the trial. The study indicated that oral probiotic adjunctive treatment did not increase the cure rate of Chinese BV patients compared to metronidazole.