Homemade blenderized tube feeding improves gut microbiome communities in children with enteral nutrition

Enteral nutrition for children is supplied through nasogastric or gastrostomy tubes. Diet not only influences nutritional intake but also interacts with the composition and function of the gut microbiota. Homemade blenderized tube feeding has been administered to children receiving enteral nutrition, in addition to ready-made tube feeding. The purpose of this study was to evaluate the oral/gut microbial communities in children receiving enteral nutrition with or without homemade blenderized tube feeding. Among a total of 30 children, 6 receiving mainly ready-made tube feeding (RTF) and 5 receiving mainly homemade blenderized tube feeding (HBTF) were analyzed in this study. Oral and gut microbiota community profiles were evaluated through 16S rRNA sequencing of saliva and fecal samples. The α-diversity representing the number of observed features, Shannon index, and Chao1 in the gut were significantly increased in HBTF only in the gut microbiome but not in the oral microbiome. In addition, the relative abundances of the phylum Proteobacteria, class Gammaproteobacteria, and genus Escherichia-Shigella were significantly low, whereas that of the genus Ruminococcus was significantly high in the gut of children with HBTF, indicating HBTF altered the gut microbial composition and reducing health risks. Metagenome prediction showed enrichment of carbon fixation pathways in prokaryotes at oral and gut microbiomes in children receiving HBTF. In addition, more complex network structures were observed in the oral cavity and gut in the HBTF group than in the RTF group. In conclusion, HBTF not only provides satisfaction and enjoyment during meals with the family but also alters the gut microbial composition to a healthy state

Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients

Endotoxemia by Porphyromonas gingivalis Injection Aggravates Non-alcoholic Fatty Liver Disease, Disrupts Glucose/Lipid Metabolism, and Alters Gut Microbiota in Mice

Many risk factors related to the development of non-alcoholic fatty liver disease (NAFLD) have been proposed, including the most well-known of diabetes and obesity as well as periodontitis. As periodontal pathogenic bacteria produce endotoxins, periodontal treatment can result in endotoxemia. The aim of this study was to investigate the effects of intravenous, sonicated Porphyromonas gingivalis (Pg) injection on glucose/lipid metabolism, liver steatosis, and gut microbiota in mice. Endotoxemia was induced in C57BL/6J mice (8 weeks old) by intravenous injection of sonicated Pg; Pg was deactivated but its endotoxin remained. The mice were fed a high-fat diet and administered sonicated Pg (HFPg) or saline (HFco) injections for 12 weeks. Liver steatosis, glucose metabolism, and gene expression in the liver were evaluated. 16S rRNA gene sequencing with metagenome prediction was performed on the gut microbiota. Compared to HFco mice, HFPg mice exhibited impaired glucose tolerance and insulin resistance along with increased liver steatosis. Liver microarray analysis demonstrated that 1278 genes were differentially expressed between HFco and HFPg mice. Gene set enrichment analysis showed that fatty acid metabolism, hypoxia, and TNFα signaling via NFκB gene sets were enriched in HFPg mice. Although sonicated Pg did not directly reach the gut, it changed the gut microbiota and decreased bacterial diversity in HFPg mice. Metagenome prediction in the gut microbiota showed enriched citrate cycle and carbon fixation pathways in prokaryotes. Overall, intravenous injection of sonicated Pg caused impaired glucose tolerance, insulin resistance, and liver steatosis in mice fed high-fat diets. Thus, blood infusion of Pg contributes to NAFLD and alters the gut microbiota

Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis

A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease

Novel Flowchart Guiding the Non-Surgical and Surgical Management of Peri-Implant Complications: A Narrative Review

Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are induced by dysbiotic microbiota resulting in the inflammatory destruction of peri-implant tissue. Nonetheless, there has yet to be an established protocol for the treatment of these diseases in a predictable manner, although many clinicians and researchers have proposed various treatment modalities for their management. With the increase in the number of reports evaluating the efficacy of various treatment modalities and new materials, the use of multiple decontamination methods to clean infected implant surfaces is recommended; moreover, the use of hard tissue laser and/or air abrasion techniques may prove advantageous in the future. Limited evidence supports additional effects on clinical improvement in antimicrobial administration for treating peri-implantitis. Implantoplasty may be justified for decontaminating the implant surfaces in the supracrestal area. Surgical treatment is employed for advanced peri-implantitis, and appropriate surgical methods, such as resection therapy or combination therapy, should be selected based on bone defect configuration. This review presents recent clinical advances in debridement methods for contaminated implant surfaces and regenerative materials for treating peri-implant bone defects. It also proposes a new flowchart to guide the treatment decisions for peri-implant disease

Functional dysbiosis within dental plaque microbiota in cleft lip and palate patients

Abstract Background Dental caries is a polymicrobial disease and prevalent among cleft lip and palate (CLP) patients, although their oral hygiene is well maintained. Dysbiosis, the state of imbalance within the dental plaque microbiota, may cause caries prevalence among these patients. However, little is known about how dysbiosis occurs and affects cariogenicity. To find dysbiotic signs, here we conducted a metatranscriptomic analysis for the plaque microbiota in six CLP patients and four controls. Methods Total bacterial RNA was extracted from each sample and sequenced. Bacterial composition and functional profiles were estimated from 16S rRNA and mRNA reads, respectively. The mRNA reads were further used for estimating bacterial composition. Species listed in both rRNA-based and mRNA-based bacterial composition were identified as viable taxa with in situ function (VTiF), and the VTiF with a high mRNA-to-rRNA ratio were considered to be transcriptionally active. A network was constructed for each group by connecting two VTiF if their mRNA abundances were positively correlated. Results The bacterial composition and functional profiles themselves did not provide remarkable signs of dysbiosis in the CLP group. However, the group-specific active taxa were identified, including streptococcal and Prevotella species in the CLP group. Moreover, the network structure was different between groups; Actinomyces johnsonii and several species in the CLP group were the active taxa, which were connected based on positive correlations with statistical significance. Conclusions Functional dysbiosis within the plaque microbiota was observed such as difference of the network structure between groups, and may be associated with cariogenicity. The observed functional dysbiosis was an invisible change within the microbiota in the oral cavity of CLP patients. This may emphasize the importance of maintaining good oral hygiene of the patients with cleft anomalies

Distinct interacting core taxa in co-occurrence networks enable discrimination of polymicrobial oral diseases with similar symptoms

Polymicrobial diseases, which can be life threatening, are caused by the presence and interactions of multiple microbes. Peri-implantitis and periodontitis are representative polymicrobial diseases that show similar clinical symptoms. To establish a means of differentiating between them, we compared microbial species and functional genes in situ by performing metatranscriptomic analyses of peri-implantitis and periodontitis samples obtained from the same subjects (n = 12 each). Although the two diseases differed in terms of 16S rRNA-based taxonomic profiles, they showed similarities with respect to functional genes and taxonomic and virulence factor mRNA profiles. The latter—defined as microbial virulence types—differed from those of healthy periodontal sites. We also showed that networks based on co-occurrence relationships of taxonomic mRNA abundance (co-occurrence networks) were dissimilar between the two diseases. Remarkably, these networks consisted mainly of taxa with a high relative mRNA-to-rRNA ratio, with some showing significant co-occurrence defined as interacting core taxa, highlighting differences between the two groups. Thus, peri-implantitis and periodontitis have shared as well as distinct microbiological characteristics. Our findings provide insight into microbial interactions in polymicrobial diseases with unknown etiologies