Helicobacter pylori infection in infant rhesus macaque monkeys is associated with an altered lung and oral microbiome.

It is estimated that more than half of the world population has been infected with Helicobacter pylori. Most newly acquired H. pylori infections occur in children before 10 years of age. We hypothesized that early life H. pylori infection could influence the composition of the microbiome at mucosal sites distant to the stomach. To test this hypothesis, we utilized the infant rhesus macaque monkey as an animal model of natural H. pylori colonization to determine the impact of infection on the lung and oral microbiome during a window of postnatal development. From a cohort of 4-7 month-old monkeys, gastric biopsy cultures identified 44% of animals infected by H. pylori. 16S ribosomal RNA gene sequencing of lung washes and buccal swabs from animals showed distinct profiles for the lung and oral microbiome, independent of H. pylori infection. In order of relative abundance, the lung microbiome was dominated by the phyla Proteobacteria, Firmicutes, Bacteroidota, Fusobacteriota, Campilobacterota and Actinobacteriota while the oral microbiome was dominated by Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota. In comparison to the oral cavity, the lung was composed of more genera and species that significantly differed by H. pylori status, with a total of 6 genera and species that were increased in H. pylori negative infant monkey lungs. Lung, but not plasma IL-8 concentration was also associated with gastric H. pylori load and lung microbial composition. We found the infant rhesus macaque monkey lung harbors a microbiome signature that is distinct from that of the oral cavity during postnatal development. Gastric H. pylori colonization and IL-8 protein were linked to the composition of microbial communities in the lung and oral cavity. Collectively, these findings provide insight into how H. pylori infection might contribute to the gut-lung axis during early childhood and modulate future respiratory health.

Helicobacter pylori Infection in Infant Rhesus Macaque Monkeys is Associated with an Altered Lung and Oral Microbiome.

Background: It is estimated that more than half of the world population has been infected with Helicobacter pylori. Most newly acquired H. pylori infections occur in children before 10 years of age. We hypothesized that early life H. pylori infection could influence the composition of the microbiome at mucosal sites distant to the stomach. To test this hypothesis, we utilized the infant rhesus macaque monkey as an animal model of natural H. pylori colonization to determine the impact of infection on the lung and oral microbiome during a window of postnatal development. Results: From a cohort of 4-7-month-old monkeys, gastric biopsy cultures identified 44% of animals infected by H. pylori. 16S ribosomal RNA gene sequencing of lung washes and buccal swabs from animals showed distinct profiles for the lung and oral microbiome, independent of H. pylori infection. In relative order of abundance, the lung microbiome was dominated by the phyla Proteobacteria, Firmicutes, Bacteroidota, Fusobacteriota, Campilobacterota and Actinobacteriota while the oral microbiome was dominated by Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota. Relative to the oral cavity, the lung was composed of more genera and species that significantly differed by H. pylori status, with a total of 6 genera and species that were increased in H. pylori negative infant monkey lungs. Lung, but not plasma IL-8 concentration was also associated with gastric H. pylori load and lung microbial composition. Conclusions: We found the infant rhesus macaque monkey lung harbors a microbiome signature that is distinct from that of the oral cavity during postnatal development. Gastric H. pylori colonization and IL-8 protein were linked to the composition of microbial communities in the lung and oral cavity. Collectively, these findings provide insight into how H. pylori infection might contribute to the gut-lung axis during early childhood and modulate future respiratory health.

Functional analysis of the relationship between intestinal microbiota and the expression of hepatic genes and pathways during the course of liver regeneration.

BACKGROUND & AIMS: The pathways regulating liver regeneration have been extensively studied within the liver. However, the signaling contribution derived from the gut microbiota to liver regeneration is poorly understood. METHODS: Microbiota and expression of hepatic genes in regenerating livers obtained from mice at 0h to 9days post 2/3 partial hepatectomy were temporally profiled to establish their interactive relationships. RESULTS: Partial hepatectomy led to rapid changes in gut microbiota that was reflected in an increased abundance of Bacteroidetes S24-7 and Rikenellaceae and decreased abundance of Firmicutes Clostridiales, Lachnospiraceae, and Ruminococcaceae. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to infer biological functional changes of the shifted microbiota. RNA-sequencing data revealed 6125 genes with more than a 2-fold difference in their expression levels during regeneration. By analyzing their expression pattern, six uniquely expressed patterns were observed. In addition, there were significant correlations between hepatic gene expression profiles and shifted bacterial populations during regeneration. Moreover, hepatic metabolism and immune function were closely associated with the abundance of Ruminococcacea, Lachnospiraceae, and S24-7. Bile acid profile was analyzed because bacterial enzymes produce bile acids that significantly impact hepatocyte proliferation. The data revealed that specific bacteria were closely associated with the concentration of certain bile acids and expression of hepatic genes. CONCLUSIONS: The presented data established, for the first time, an intimate relationship between intestinal microbiota and the expression of hepatic genes in regenerating livers.

Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis.

BACKGROUND: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis. METHODS: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS). RESULTS: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1ß-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-ß in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen. CONCLUSIONS: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.