The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD.

Fungal rhinosinusitis is a unique phenotype of chronic rhinosinusitis with unique clinical and histological characteristics. The role of bacterial microbiota in various phenotypes chronic rhinosinusitis is not thoroughly understood. Therefore, we conducted 16s rRNA amplification sequencing to determine differences in bacterial communities between phenotypes (fungal vs. non- fungal) and anatomical sites (middle meatus vs. nasopharynx). Endoscope-guided swabs were used to collect samples from the middle meatus and nasopharynx of seven consecutive patients with fungal and 18 consecutive patients with non-fungal rhinosinusitis. DNA was extracted and investigated through 16S rRNA amplification. Among samples from the middle meatus, Shannon diversity was significantly lower in those from the fungal rhinosinusitis group (p = 0.029). However, no significant differences in diversity were noted between nasopharynx samples (p = 0.85). Fungal rhinosinusitis samples exhibited a distinct distribution of taxon relative abundance, which involved not only the absence of rhinosinusitis-associated commensal Corynebacterium and Fusobacterium in the middle meatus but also a significant increase in Haemophilus prevalence and abundance. This is the first study to compare bacterial communities in fungal and non-fungal rhinosinusitis samples. Our findings demonstrated that bacterial community dysbiosis was more apparent in fungal rhinosinusitis samples and was limited to the middle meatus.

Autoimmune pancreatitis (AIP) is a chronic fibro-inflammatory disorder of the pancreas. Recent clinicopathological analysis revealed that most cases of AIP are pancreatic manifestations of systemic IgG4-related disease (IgG4-RD), a newly established disease characterized by enhanced IgG4 antibody responses and the involvement of multiple organs. Although the immuno-pathogenesis of AIP and IgG4-RD has been poorly defined, we recently showed that activation of plasmacytoid dendritic cells (pDCs) with the ability to produce large amounts of IFN-α and IL-33 mediates chronic fibro-inflammatory responses in experimental and human AIP. Moreover, M2 macrophages producing a large amount of IL-33 play pathogenic roles in the development of human IgG4-RD. Interestingly, recent studies including ours provide evidence that compositional alterations of gut microbiota are associated with the development of human AIP and IgG4-RD. In addition, intestinal dysbiosis plays pathological roles in the development of chronic pancreatic inflammation as dysbiosis mediates the activation of pDCs producing IFN-α and IL-33, thereby causing experimental AIP. In this Mini Review, we focus on compositional alterations of gut microbiota in AIP and IgG4-RD to clarify the mechanisms by which intestinal dysbiosis contributes to the development of these disorders.

We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis.

Functional dyspepsia (FD) is one of the most prevalent chronic functional gastrointestinal disorders. Several distinct pathophysiological mechanisms, including gastro duodenal motor disorders, visceral hypersensitivity, brain-gut interactions, duodenal subtle inflammation, and genetic susceptibility, have been implicated in the pathogenesis of the disease, so far. However, emerging evidence suggests that both quantitative and qualitative disturbances of the gastrointestinal microbiota may also be implicated. In this context, several studies have demonstrated differences of the commensal bacterial community between patients with FD and healthy controls, while others have shown that intestinal dysbiosis might associate with disease's symptoms severity. Elucidating these complex interactions constituting the microbiota and host crosstalk, may eventually lead to the discovery of novel, targeted therapeutic approaches that may be efficacious in treating the multiple aspects of the disorder. In this review, we summarize the data of the latest research with focus on the association between gut microbiota alterations and host regarding the pathogenesis of FD.

The prevalence of urinary stone disease (USD) is rapidly rising. However, the factors driving this increase are unknown. Recent microbiome studies suggest that dysbiosis may in part contribute to the increasing prevalence. The objective of the current study was to determine the nature and location of dysbiosis associated with USD. We conducted microbiome analysis from the gastrointestinal and urinary tracts, along with a metabolomic analysis of the urinary metabolome, from subjects with an active episode of USD or no history of the disease. Higher rates of antibiotic use among USD patients along with integrated microbiome and metabolomic results support the hypothesis that USD is associated with an antibiotic-driven shift in the microbiome from one that protects against USD to one that promotes the disease. Specifically, our study implicates urinary tract Lactobacillus and Enterobacteriaceae in protective and pathogenic roles for USD, respectively, which conventional, culture-based methods of bacterial analysis from urine and kidney stones would not necessarily detect. Results suggest that antibiotics produce a long-term shift in the microbiome that may increase the risk for USD, with the urinary tract microbiome holding more relevance for USD than the gut microbiome.

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease in humans and is characterized by the presence of hyperactive immune cells and aberrant antibody responses to nuclear and cytoplasmic antigens, including characteristic anti-double-stranded DNA antibodies. We performed a cross-sectional study in order to determine if an SLE-associated gut dysbiosis exists in patients without active disease. A group of 20 SLE patients in remission, for which there was strict inclusion and exclusion criteria, was recruited, and we used an optimized Ion Torrent 16S rRNA gene-based analysis protocol to decipher the fecal microbial profiles of these patients and compare them with those of 20 age- and sex-matched healthy control subjects. We found diversity to be comparable based on Shannon's index. However, we saw a significantly lower Firmicutes/Bacteroidetes ratio in SLE individuals (median ratio, 1.97) than in healthy subjects (median ratio, 4.86; P < 0.002). A lower Firmicutes/Bacteroidetes ratio in SLE individuals was corroborated by quantitative PCR analysis. Notably, a decrease of some Firmicutes families was also detected. This dysbiosis is reflected, based on in silico functional inference, in an overrepresentation of oxidative phosphorylation and glycan utilization pathways in SLE patient microbiota.

The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis.

The vaginal microbiota dysbiosis is closely associated with the development of reproductive diseases. However, the contribution of mycobiome to intrauterine adhesion (IUA) disease remains unknown. Harnessing 16S and ITS2 rDNA sequencing analysis, we investigate both bacterial and fungal microbiota compositions across 174 samples taken from both cervical canal (CC) and middle vagina (MV) sites of IUA patients. Overall, there is no significant difference in microbial diversity between healthy subjects (HS) and IUA patients. However, we observe the IUA-specific bacterial alterations such as increased Dialister and decreased Bifidobacterium and enriched fungal genera like increased Filobasidium and Exophiala. Moreover, site-specific fungal-bacterial correlation networks are discovered in both CC and MV samples of IUA patients. Mechanistic investigation shows that Candida parapsilosis, other than Candida albicans and Candida maltosa, prevents the exacerbation of inflammatory activities and fibrosis, and modulates bacterial microbiota during IUA progression in a rat model of IUA. Our study thus highlights the importance of mycobiota in IUA progression, which may facilitate the development of therapeutic target for IUA prevention. IMPORTANCE Intrauterine adhesion (IUA) often leads to hypomenorrhea, amenorrhea, repeat miscarriages, and infertility. It has been prevalent over the last few decades in up to 13% of women who experience pregnancy termination during the first trimester, and 30% of women undergo dilation and curettage after a late, spontaneous abortion. However, the pathogenesis of IUA remains unclear. Despite reports of microbiota dysbiosis during IUA progression, there is little information on the effect of fungal microbiota on the development of IUA. This study not only enhances our understanding of the mycobiome in IUA patients but also provides potential intervention strategies for prevention of IUA by targeting mycobiome.

Sepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied.

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB-IV tumor-node-metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB-IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers. SIGNIFICANCE: Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis.See related commentary by Zitvogel and Kroemer, p. 224.This article is highlighted in the In This Issue feature, p. 211.

Systemic inflammatory response syndrome (SIRS) is a severe condition characterized by systemic inflammation, which may lead to multiple organ failure, shock and death. SIRS is common in burn patients, pancreatitis and sepsis. SIRS is often accompanied by intestinal dysbiosis. However, the mechanism, role and details of microbiome alterations during the early phase of acute SIRS are not completely understood. The current study aimed to characterize the dynamic alterations of both the intestinal and respiratory microbiome at two timepoints during the early phase of acute SIRS (4 and 8 h after LPS) and link these to the host response in a mouse model of a LPS-induced lethal SIRS. Acute SIRS had no effect on the microbiome in the large intestine but induced a rapid dysbiosis in the small intestine, which resembled the microbiome alterations commonly observed in SIRS patients. Later in the disease progression, a dysbiosis of the respiratory microbiome was observed, which was associated with the MMP9 expression in the lungs. Although similar bacteria were increased in both the lung and the small intestine, no evidence for a gut-lung translocation was observed. Gut dysbiosis is commonly observed in diseases involving inflammation in the gut. However, whether the inflammatory response associated with SIRS and sepsis can directly cause gut dysbiosis was still unclear. In the current study we provide evidence that a LPS-induced SIRS can directly cause dysbiosis of the small intestinal and respiratory microbiome.

To dissect potential confounding effects of breast milk and formula feeding on crying + fussing, fecal calprotectin, and gut microbiota in babies with colic. We hypothesized that infant colic is associated with gut inflammation linked to intestinal dysbiosis.

Oral microbiota has largely escaped attention in Parkinson's disease (PD), despite its pivotal role in maintaining oral and systemic health.

Individuals with cystic fibrosis (CF) often experience gastrointestinal (GI) abnormalities. In recent years, the intestinal microbiome has been postulated as a contributor to the development of CF-associated GI complications, hence representing a potential therapeutic target for treatment. We recently developed a rabbit model of CF, which is shown to manifest many human patient-like pathological changes, including intestinal obstruction. Here, we investigated the feces microbiome in young CF rabbits in the absence of antibiotics treatment. Stool samples were collected from seven- to nine-week-old CF rabbits (n = 7) and age-matched wild-type (WT) rabbits (n = 6). Microbiomes were investigated by iTag sequencing of 16S rRNA genes, and functional profiles were predicted using PICRUSt. Consistent with reports of those in pediatric CF patients, the fecal microbiomes of CF rabbits are of lower richness and diversity than that of WT rabbits, with a marked taxonomic and inferred functional dysbiosis. Our work identified a new CF animal model with the manifestation of intestinal dysbiosis phenotype. This model system may facilitate the research and development of novel treatments for CF-associated gastrointestinal diseases.

The gastric microbiome has been proposed as an etiological factor in gastric carcinogenesis. We compared the gastric microbiota in subjects presenting with gastric cancer (GC, n = 12) and controls (functional dyspepsia (FD), n = 20) from a high GC risk population in Singapore and Malaysia. cDNA from 16S rRNA transcripts were amplified (515F-806R) and sequenced using Illumina MiSeq 2 × 250 bp chemistry. Increased richness and phylogenetic diversity but not Shannon's diversity was found in GC as compared to controls. nMDS clustered GC and FD subjects separately, with PERMANOVA confirming a significant difference between the groups. H. pylori serological status had a significant impact on gastric microbiome α-diversity and composition. Several bacterial taxa were enriched in GC, including Lactococcus, Veilonella, and Fusobacteriaceae (Fusobacterium and Leptotrichia). Prediction of bacterial metabolic contribution indicated that serological status had a significant impact on metabolic function, while carbohydrate digestion and pathways were enriched in GC. Our findings highlight three mechanisms of interest in GC, including enrichment of pro-inflammatory oral bacterial species, increased abundance of lactic acid producing bacteria, and enrichment of short chain fatty acid production pathways.

Little is known about the relationship between gut dysbiosis, inflammation, and adverse outcomes in patients with chronic kidney disease. We examined the association of microbial diversity with all-cause mortality in hemodialysis patients. The gut microbiota was assessed by 16S ribosomal RNA gene sequencing. During a median follow-up of 2.1 years, the adjusted risk of death among patients with higher diversity (above median) was 74% lower than that among patients with lower diversity (below median). We then compared the microbial composition between nonsurvivors and survivors in a matched case-control study. We observed significantly lower microbial diversity and higher proinflammatory cytokines among nonsurvivors than survivors. Specifically, the relative abundance of Succinivibrio and Anaerostipes, two short-chain fatty acid-producing bacteria, was markedly reduced in nonsurvivors. Thus, a unique gut microbial composition is associated with an increased risk of mortality among hemodialysis patients and may be used to identify subjects with a poor prognosis.

There is high morbidity in clinical patients with duodenum bulb inflammation. Mucosa-associated microbiota, which are closely related to inflammatory processes, may have a pathogenic role, but the duodenum bulb microbial signature is poorly studied.

HPV persistent infection is a main event leading to the development of cervical intraepithelial neoplasia and cervical cancer. Earlier to distinguish HPV persistent and transient infection is meaningful but the methods are limited. This study used 16S rDNA sequencing to determine the cervicovaginal microbiota of HPV persistent infection, transient infection and health women. Sequences analysis was performed and according to subsequent statistical analysis, the structure of cervicovaginal microbiota of healthy and transient infection individuals is relatively single, Firmicutes occupy the main composition. However, that of the HPV persistent infection presented a complicated trend and the abundance of Proteobacteria, Actinobacteria, Bacteroidetes and Fusobacteria was higher. The significance p-values of the average species abundance of Firmicutes, Proteobacteria and Bacteroides between HPV persistent and transient infection groups were 0.003, 0.018 and 0.005, respectively. The study also found 36 biomarkers of cervicovaginal microbiota dysbiosis for LDA score>4 among different groups. At genus level, Prevotella, Sphingomonas and Anaerococcus correlated with HPV persistent infection. At species level, Lactobacillus iners correlated with HPV transient infection. Besides, local immune microenvironment was changed with cervicovaginal microbiota dysbiosis. Interleukin-6 and TNF-α were significantly upregulated in cervical secretions from HPV persistent infection compared with those from transient infection and healthy women. Peripheral blood Regulatory T cells and myeloid-derived suppressor cells in patients with HPV persistent infection were also significantly increased. In conclusion, this study identified cervicovaginal microbiota dysbiosis closely related to HPV persistent infection, which provided a new idea and method for the prevention of cervical cancer.

IgA nephropathy (IgAN) is reportedly associated with microbial dysbiosis. However, the microbiome dysregulation of IgAN patients across multiple niches remains unclear. To gain a systematic understanding of microbial dysbiosis, we conducted large-scale 16S rRNA gene sequencing in IgAN patients and healthy volunteers across 1,732 oral, pharynx, gut, and urine samples. We observed a niche-specific increase of several opportunistic pathogens, including Bergeyella and Capnocytophaga in the oral and pharynx, whereas some beneficial commensals decreased in IgAN patients. Similar alterations were also observed in the early versus advanced stage of chronic kidney disease (CKD) progression. Moreover, Bergeyella, Capnocytophaga, and Comamonas in the oral and pharynx were positively associated with creatinine and urea, indicating renal lesions. Random forest classifiers were developed by using the microbial abundance to predict IgAN, achieving an optimal accuracy of 0.879 in the discovery phase and 0.780 in the validation phase. IMPORTANCE This study provides microbial profiles of IgAN across multiple niches and underlines the potential of these biomarkers as promising, noninvasive tools with which to differentiate IgAN patients for clinical applications.