Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.

Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis.

OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.

A metagenome-wide association study of gut microbiota in asthma in UK adults.

BACKGROUND: Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults. RESULTS: The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients. CONCLUSION: In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.

A genome-wide association study reveals the relationship between human genetic variation and the nasal microbiome.

The nasal cavity harbors diverse microbiota that contributes to human health and respiratory diseases. However, whether and to what extent the host genome shapes the nasal microbiome remains largely unknown. Here, by dissecting the human genome and nasal metagenome data from 1401 healthy individuals, we demonstrated that the top three host genetic principal components strongly correlated with the nasal microbiota diversity and composition. The genetic association analyses identified 63 genome-wide significant loci affecting the nasal microbial taxa and functions, of which 2 loci reached study-wide significance (p < 1.7 × 10-10): rs73268759 within CAMK2A associated with genus Actinomyces and family Actinomycetaceae; and rs35211877 near POM121L12 with Gemella asaccharolytica. In addition to respiratory-related diseases, the associated loci are mainly implicated in cardiometabolic or neuropsychiatric diseases. Functional analysis showed the associated genes were most significantly expressed in the nasal airway epithelium tissue and enriched in the calcium signaling and hippo signaling pathway. Further observational correlation and Mendelian randomization analyses consistently suggested the causal effects of Serratia grimesii and Yokenella regensburgei on cardiometabolic biomarkers (cystine, glutamic acid, and creatine). This study suggested that the host genome plays an important role in shaping the nasal microbiome.

Endovascular treatment of acute basilar artery occlusion: A systematic review and meta-analysis of first-line stent retriever versus direct aspiration.

BACKGROUND: The best choice between first-line aspiration and stent retriever for acute basilar artery occlusion remains controversial. This study aims to perform a systematic review and meta-analysis comparing the stent retriever and direct aspiration about reported recanalization rates and periprocedural complications. METHOD: PubMed, Embase, Web of Science, Cochrane, and Clinical Trials were searched for the studies evaluating the efficacy and safety of first-line aspiration versus stent retriever for acute basilar artery occlusion. A standard software program (Stata Corporation) was used for end-point analyses. Statistical significance was defined as a p-value less than .05. RESULTS: A total of 11 studies were involved in the current study, including 1014 patients. Regarding postoperative recanalization, the pooled analysis identified a significant difference in successful recanalization (odds ratio [OR] = 1.642; 95% confidence interval (95% CI): 1.099-2.453; p = .015) and complete recanalization (OR = 3.525; 95% CI: 1.306-2.872; p = .001) between the two groups in favor of the first-line aspiration. Concerning the complications, the first-line aspiration could achieve a lower rate of total complication (OR = .359; 95% CI: .229-.563; p < .001) and hemorrhagic complication (OR = .446, 95% CI: .259-.769; p = .004) than stent retriever. No significant difference was observed in postoperative mortality (OR = .966; p = .880), subarachnoid hematoma (OR = .171; p = .094), and parenchymal hematoma (OR = .799; p = .720). In addition, the pooled results revealed a significant difference in procedure duration between the two groups in favor of aspiration (WMD = -27.630, 95% CI: -50.958 to -4.302; p = .020). However, there was no significant difference in favorable outcome (OR = 1.149; p = .352) and rescue therapy (OR = 1.440; p = .409) between the two groups. CONCLUSION: Given that the first-line aspiration was associated with a higher rate of postoperative recanalization, a lower risk of postoperative complication, and a faster duration of the procedure, these findings support the aspiration may be more secure than a stent retriever.

Integrated Human Skin Bacteria Genome Catalog Reveals Extensive Unexplored Habitat-Specific Microbiome Diversity and Function.

The skin is the largest organ in the human body. Various skin environments on its surface constitutes a complex ecosystem. One of the characteristics of the skin micro-ecosystem is low biomass, which greatly limits a comprehensive identification of the microbial species through sequencing. In this study, deep-shotgun sequencing (average 21.5 Gigabyte (Gb)) from 450 facial samples and publicly available skin metagenomic datasets of 2069 samples to assemble a Unified Human Skin Genome (UHSG) catalog is integrated. The UHSG encompasses 813 prokaryotic species derived from 5779 metagenome-assembled genomes, among which 470 are novel species covering 20 phyla with 1385 novel assembled genomes. Based on the UHSG, the core functions of the skin microbiome are described and the differences in amino acid metabolism, carbohydrate metabolism, and drug resistance functions among different phyla are identified. Furthermore, analysis of secondary metabolites of the near-complete genomes further find 1220 putative novel secondary metabolites, several of which are found in previously unknown genomes. Single nucleotide variant (SNV) reveals a possible skin protection mechanism: the negative selection process of the skin environment to conditional pathogens. UHSG offers a convenient reference database that will facilitate a more in-depth understanding of the role of skin microorganisms in the skin.

Sex differences in the oral microbiome, host traits, and their causal relationships.

The oral microbiome has been implicated in a growing number of diseases; however, determinants of the oral microbiome and their roles remain elusive. Here, we investigated the oral (saliva and tongue dorsum) metagenome, the whole genome, and other omics data in a total of 4,478 individuals and demonstrated that the oral microbiome composition and its major contributing host factors significantly differed between sexes. We thus conducted a sex-stratified metagenome-genome-wide-association study (M-GWAS) and identified 11 differential genetic associations with the oral microbiome (p sex-difference  < 5 × 10-8). Furthermore, we performed sex-stratified Mendelian randomization (MR) analyses and identified abundant causalities between the oral microbiome and serum metabolites. Notably, sex-specific microbes-hormonal interactions explained the mostly observed sex hormones differences such as the significant causalities enrichments for aldosterone in females and androstenedione in males. These findings illustrate the necessity of sex stratification and deepen our understanding of the interplay between the oral microbiome and serum metabolites.

Correlation between human papillomavirus infection and reproduction.

Human papillomavirus (HPV) is one of the most common sexually transmitted infectious viruses among men and women of reproductive age throughout the world. Pregnant women are susceptible during pregnancy and most infections of them are self-limiting infections, which can be removed by their autoimmunity, while the persistent infections are associated with precancerous lesions and cancer of the anogenital mucosa in women and men. In addition, HPV infection may also affect reproductive health and fertility. The effect of HPV on female fertility requires further study, but HPV influences sperm parameters. Furthermore, whether HPV infection alters the effect of assisted reproductive technology and whether there is an association between it and assisted reproductive technology (ART) outcomes is unknown. It is considered that the relationship between HPV infection and spontaneous abortion (SA), assisted reproductive technology (ART) outcomes and spontaneous preterm birth (sPTB) has profound implications for the medical care of pregnant and infertile women. This paper reviews the relationship between human papillomavirus infection during pregnancy and SA, sPTB and ART in reproduction, and reviews the relationship between human papillomavirus and human fertility by summarizing the recent domestic and foreign literature.

Effect of Laparoscopic Total Extraperitoneal Umbilical Hernia Repair on Incision Infection, Complication Rate, and Recurrence Rate in Patients with Umbilical Hernia.

The aim of this study is to clarify the influence of laparoscopic total extraperitoneal umbilical hernia repair on incision infection, complication rate, and recurrence rate in patients with an umbilical hernia (UH). Sixty-seven UH patients referred to our hospital from June 2017 to June 2019 were selected as the research participants. Thirty-six patients in the research group (RG) were treated with laparoscopic total extraperitoneal umbilical hernia repair, and the other 31 cases in the control group (CG) were treated with traditional umbilical hernia repair. The two cohorts of patients were compared with respect to the curative effect after treatment; intraoperative blood loss, operation time, postoperative pain time, ambulation time, and hospital stay; incidence of complications; pain severity (VAS) before and after operation; sleep quality (PSQI) before and after operation; patient satisfaction after treatment; and recurrence half a year after discharge. The RG presented a higher effective treatment rate (P < 0.05), less intraoperative blood loss, operation time, postoperative pain time, ambulation time, and hospital stay, as well as lower incidence of complications than the CG (P < 0.05). VAS and PSQI scores differed insignificantly between the two cohorts of patients before treatment (P > 0.05) but reduced after treatment, with lower VAS and PSQI scores in the RG than in the CG (P < 0.05). The number of people who were highly satisfied, as investigated by the satisfaction survey, was higher in the RG than in the CG, while the recurrence rate of prognosis was lower than that in the CG (P < 0.05). Laparoscopic total extraperitoneal umbilical hernia repair is effective for UH patients and can validly reduce the incidence of complications and recurrence rate, which has huge clinical application value.

Stressful events induce long-term gut microbiota dysbiosis and associated post-traumatic stress symptoms in healthcare workers fighting against COVID-19.

OBJECTIVE: The microbiota-gut-brain axis is a key pathway perturbed by prolonged stressors to produce brain and behavioral disorders. Frontline healthcare workers (FHWs) fighting against COVID-19 typically experience stressful event sequences and manifest some mental symptoms; however, the role of gut microbiota in such stress-induced mental problems remains unclear. We investigated the association between the psychological stress of FHW and gut microbiota. METHODS: We used full-length 16S rRNA gene sequencing to characterize the longitudinal changes in gut microbiota and investigated the impact of microbial changes on FHWs' mental status. RESULTS: Stressful events induced significant depression, anxiety, and stress in FHWs and disrupted the gut microbiome; gut dysbiosis persisted for at least half a year. Different microbes followed discrete trajectories during the half-year of follow-up. Microbes associated with mental health were mainly Faecalibacterium spp. and [Eubacterium] eligens group spp. with anti-inflammatory effects. Of note, the prediction model indicated that low abundance of [Eubacterium] hallii group uncultured bacterium and high abundance of Bacteroides eggerthii at Day 0 (immediately after the two-month frontline work) were significant determinants of the reappearance of post-traumatic stress symptoms in FHWs. LIMITATIONS: The lack of metabolomic evidence and animal experiments result in the unclear mechanism of gut dysbiosis-related stress symptoms. CONCLUSION: The stressful event sequences of fighting against COVID-19 induce characteristic longitudinal changes in gut microbiota, which underlies dynamic mental state changes.

Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omes.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, as well as cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancyhistory, delivery history, cesarean section, and breastfeeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breastfeeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiomes, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Linking gut microbiome to bone mineral density: a shotgun metagenomic dataset from 361 elderly women.

Bone mass loss contributes to the risk of bone fracture in the elderly. Many factors including age, obesity, estrogen and diet, are associated with bone mass loss. Mice studies suggested that the gut microbiome might affect the bone mass by regulating the immune system. However, there has been little evidence from human studies. Bone loss increases after menopause. Therefore, we have recruited 361 Chinese post-menopausal women to collect their fecal samples and metadata to conduct a metagenome-wide association study (MWAS) to investigate the influence of the gut microbiome on bone health. Gut microbiome sequencing data were produced using the BGISEQ-500 sequencer. Bone mineral density (BMD) was calculated using a Hologic dual energy X-ray machine, and body mass index (BMI) and age were also recorded. This collected data allows exploration of the gut microbial diversity and their links to bone mass loss as well as to microbial markers for bone mineral density. In addition, these data are potentially useful in studying the role that the gut microbiota might play in bone mass loss and in exploring the process of bone mass loss.

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome.

The oral microbiota contains billions of microbial cells, which could contribute to diseases in many body sites. Challenged by eating, drinking, and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1915 individuals, for both the tongue dorsum (n = 2017) and saliva (n = 1915). We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 × 10-11). Four of the five associations were well replicated in an independent cohort of 1439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of host genome-microbiome associations including six genome-wide significant associations mutually validated between the two niches. As many of the oral microbiome-associated genetic variants lie near miRNA genes, we tentatively validated the potential of host miRNAs to modulate the growth of specific oral bacteria. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk scores dominated over oral microbiome in predicting risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

Metagenome-wide association of gut microbiome features for schizophrenia.

Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis.

BACKGROUND: Early treatment is key for optimizing the therapeutic success of drugs, and the current initiating treatment that blocks the progression of bone destruction during the pre-arthritic stages remains unsatisfactory. The microbial disorder in rheumatoid arthritis (RA) patients is significantly reversed with effective treatment. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage. RESULTS: By using metagenomic shotgun sequencing and a metagenome-wide association study, we assessed the effect of Lactobacillus casei (L. casei) on the induction of arthritis as well as on the associated gut microbiota and immune disorders in adjuvant-induced arthritis (AIA) rats. Treatment of AIA rats with L. casei inhibited joint swelling, lowered arthritis scores, and prevented bone destruction. Along with the relief of arthritis symptoms, dysbiosis in the microbiome of arthritic rats was significantly reduced after L. casei intervention. The relative abundance of AIA-decreased Lactobacillus strains, including Lactobacillus hominis, Lactobacillus reuteri, and Lactobacillus vaginalis, were restored to normal and Lactobacillus acidophilus was upregulated by the administration of L. casei to the AIA rats. Moreover, L. casei downregulated the expression of pro-inflammatory cytokines, which are closely linked to the effect of the L. casei treatment-associated microbes. Functionally, the maintenance of the redox balance of oxidative stress was involved in the improvement in the L. casei-treated AIA rats. CONCLUSION: A single bacterium, L. casei (ATCC334), was able to significantly suppress the induction of AIA and protect bones from destruction in AIA rats by restoring the microbiome dysbiosis in the gut, indicating that using probiotics may be a promising strategy for treating RA, especially in the early stage of the disease.

A gene catalogue of the Sprague-Dawley rat gut metagenome.

Background: Laboratory rats such as the Sprague-Dawley (SD) rats are an important model for biomedical studies in relation to human physiological or pathogenic processes. Here we report the first catalog of microbial genes in fecal samples from Sprague-Dawley rats. Findings: The catalog was established using 98 fecal samples from 49 SD rats, divided in 7 experimental groups, and collected at different time points 30 days apart. The established gene catalog comprises 5,130,167 non-redundant genes with an average length of 750 bp, among which 64.6% and 26.7% were annotated to phylum and genus levels, respectively. Functionally, 53.1%, 21.8%,and 31% of the genes could be annotated to KEGG orthologous groups, modules, and pathways, respectively. Conclusions: A comparison of rat gut metagenome catalogue with human or mouse revealed a higher pairwise overlap between rats and humans (2.47%) than between mice and humans (1.19%) at the gene level. Ninety-seven percent of the functional pathways in the human catalog were present in the rat catalogue, underscoring the potential use of rats for biomedical research.