Controlled activation of the complement system, a key component of innate immunity, enables destruction of pathogens with minimal damage to host tissue. Complement factor H (CFH), which inhibits complement activation, and five CFH-related proteins (CFHR1-5) compose a family of structurally related molecules. Combined deletion of CFHR3 and CFHR1 is common and confers a protective effect in IgA nephropathy. Here, we report an autosomal dominant complement-mediated GN associated with abnormal increases in copy number across the CFHR3 and CFHR1 loci. In addition to normal copies of these genes, affected individuals carry a unique hybrid CFHR3-1 gene. In addition to identifying an association between these genetic observations and complement-mediated kidney disease, these results provide insight into the protective role of the combined deletion of CFHR3 and CFHR1 in IgA nephropathy.

cThis study focused on identifying reproducible effects of dietary supplementation with a mannan oligosaccharide (MOS) on the broiler cecal bacterial community structure and function in a commercial production setting. Two separate trials, each with a control and a supplemented group, were carried out in the same commercial location and run concurrently. Approximately 10,000 birds from the same commercial hatchery were mirror imaged into each of four commercial broiler sheds and fed either a control or supplemented diet. Cecal contents were obtained on days 7, 21, and 35 posthatch from 12 randomly caught broilers from each group. Bacterial pyrosequencing was performed on all samples, with approximately 250,000 sequences obtained per treatment per time point. The predominant phyla identified at all three time points in both trials were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Tenericutes, representing >99% of all sequences. MOS supplementation altered the bacterial community composition from 7 days supplementation through 35 days supplementation. Bacteroidetes appeared to be replacing Firmicutes as a result of supplementation, with the most noticeable effects after 35 days. The effects of supplementation were reproducible across both trials. PICRUSt was used to identify differences between the functional potentials of the bacterial communities as a result of MOS supplementation. Using level 3 KEGG ortholog function predictions, differences between control and supplemented groups were observed, with very strong segregation noted on day 35 posthatch in both trials. This indicated that alterations of bacterial communities as a result of MOS are likely to alter the functional capability of the cecum. The gastrointestinal microbiota plays a vital role in nutritional, physiological, and protective functions in animals (1). An understanding and a description of the intestinal microbial communities in broilers are important for the development of new feed additives and the appropriate manipulation of diets to improve broiler performance, health, and welfare (2). The intestinal microbiota has a major impact on the bioavailability and bioactivity of dietary components by consuming, storing, and circulating nutrients effectively, while also impacting the host's ability to resist infection, thereby making an essential contribution to host health and performance (3). Poor intestinal health in poultry is associated with increased susceptibility to infectious disease and colonization by pathogens (4). Bacterial-disease outbreaks impose significant constraints on poultry production, adversely impacting the poultry industry by reducing animal welfare and productivity through disease, poor digestion, and poor nutrient absorption. This, in turn, can lead to significant losses for the farmer and can increase the potential for the contamination of poultry products marketed for human consumption (5).Traditionally, antibiotics have been used in poultry feed at subtherapeutic levels to prevent clinical and subclini...

The gut microbiome has a recognized role in Non-alcoholic fatty liver disease (NAFLD) and associated comorbidities such as Type-2 diabetes and obesity. Stool transplantation has been shown to improve disease by restoring endothelial function and insulin signaling. However, more patient-friendly treatments are required. The present study aimed to test the effect of a defined bacterial consortium of nine gut commensal strains in two in vivo rodent models of Non-alcoholic steatohepatitis (NASH): a rat model of NASH and portal hypertension (PHT), and the Stelic animal (mouse) model (STAM™). In both studies the consortium was administered orally q.d. after disease induction. In the NASH rats, the consortium was administered for 2 weeks and compared to stool transplant. In the STAM™ study administration was performed for 4 weeks, and the effects compared to vehicle or Telmisartan at the stage of NASH/early fibrosis. A second group of animals was followed for another 3 weeks to assess later-stage fibrosis. In the NASH rats, an improvement in PHT and endothelial function was observed. Gut microbial compositional changes also revealed that the consortium achieved a more defined and richer replacement of the gut microbiome than stool transplantation. Moreover, liver transcriptomics suggested a beneficial modulation of pro-fibrogenic pathways. An improvement in liver fibrosis was then confirmed in the STAM™ study. In this study, the bacterial consortium improved the NAFLD activity score, consistent with a decrease in steatosis and ballooning. Serum cytokeratin-18 levels were also reduced. Therefore, administration of a specific bacterial consortium of defined composition can ameliorate NASH, PHT, and fibrosis, and delay disease progression.

Background and objective: Microbiota are thought to play a role in the development of gastric cancer (GC). Several studies have put forward putatively carcinogenic species in addition to Helicobacter pylori but are not in perfect alignment, possibly due to variable parameters in the experiments. Meta-analyses on this subject have not been published so far. Therefore, there is a lack of clinical guidance beyond H. pylori eradication therapy.Methods: Here, we analyzed gastric mucosa samples from nine public datasets, including GC samples. We defined fine grain bacterial networks of gastric mucosa and identified the species associated with the tumor status of samples.Results: Despite study-specific variability, the periodontal species Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis were found in association with tumor status in several datasets. The three species were predicted to be in interaction by ecological network analysis and also formed the intersection of tumorassociated species between four GC datasets and five colorectal cancer datasets we reanalyzed. We formulated a probiotic composition putatively competing with the GC pathogen spectrum, from correlation analysis in a large superset of gut samples (n = 17,800) from clinical-and crowd-sourced studies. Conclusions:The overlapping pathogen spectrum between two gastrointestinal tumor types, GC and colorectal cancer, has implications for etiology, treatment and prevention. In vitro testing results reported in the literature suggest H. pylori eradication treatment should be efficient against the GC pathogen spectrum, yet the existence of an upstream periodontal reservoir is of concern. To address this, we propose use of the formulated probiotics composition.

Background. Inflammatory bowel disease (IBD) is a set of conditions characterized by non-infectious chronic inflammation of the gastrointestinal tract. These primarily include Crohn's disease (CD), ulcerative colitis (UC) and indeterminate colitis. Fecal microbiota transplantation (FMT) has proven to be an effective treatment for some patients with active UC. There is currently no procedure allowing to predict the patients' response and to select the most adequate donor(s). Aim. Investigate microbiome characteristics in association with responder/non-responder status and develop selection criteria for donor samples to be used for UC FMT. Methods. Available UC longitudinal FMT microbiome data sets were in part combined and reanalyzed, with focus on species level changes in the microbiota, using state-of-the-art 16S analysis routines. Results. We predicted antibiotic resistance to be higher in non-responders (p=0.0064). Microbiomes of UC FMT responder donors have higher phylogenetic diversity (p=0.0026) and a higher proportion of facultative anaerobes (p=3.3E-5) as compared to non-responder donors. We predicted succinate and histamine to be increased in non-responder donors and non-responders, respectively. Sialic acid catabolism was also predicted to be increased in non-responder donors. Tryptamine and indole-3-acetaldehyde were predicted to be increased in responder donors. Conclusions. Our findings contribute to the establishment of selection criteria for UC FMT donor samples. Our results suggest that oxidative stress resistant facultative anaerobes are important for the establishment of an anaerobic environment and a successful UC FMT therapy. Several metabolites can be tested for additional prioritization of stool bank samples for UC FMT.