Direct research on gut microbiota for understanding its role as 'an important organ' in human individuals is difficult owing to its vast diversity and host specificity as well as ethical concerns. Transplantation of human gut microbiota into surrogate hosts can significantly facilitate the research of human gut ecology, metabolism and immunity but rodents-based model provides results with low relevance to humans. A new human flora-associated (HFA) piglet model was hereby established taking advantage of the high similarity between pigs and humans with respect to the anatomy, physiology and metabolism of the digestive system. Piglets were delivered via cesarean section into a SPF-level barrier system and were inoculated orally with a whole fecal suspension from one healthy 10-year-old boy. The establishment and composition of the intestinal microbiota of the HFA piglets were analyzed and compared with that of the human donor using enterobacterial repetitive intergenic consensus sequence-PCR fingerprinting-based community DNA hybridization, group-specific PCR-temperature gradient gel electrophoresis and real-time PCR. Molecular profiling demonstrated that transplantation of gut microbiota from a human to germfree piglets produced a donor-like microbial community with minimal individual variation. And the microbial succession with aging of those ex-germfree piglets was also similar to that observed in humans. This HFA model provides a significantly improved system for research on gut ecology in human metabolism, nutrition and drug discovery.
Objectives. We aimed to explore the impact of gut microbiota in coronary heart disease (CHD) patients through high-throughput sequencing. Methods. A total of 29 CHD in-hospital patients and 35 healthy volunteers as controls were included. Nucleic acids were extracted from fecal samples, followed by α diversity and principal coordinate analysis (PCoA). Based on unweighted UniFrac distance matrices, unweighted-pair group method with arithmetic mean (UPGMA) trees were created. Results. After data optimization, an average of 121312 ± 19293 reads in CHD patients and 234372 ± 108725 reads in controls was obtained. Reads corresponding to 38 phyla, 90 classes, and 584 genera were detected in CHD patients, whereas 40 phyla, 99 classes, and 775 genera were detected in controls. The proportion of phylum Bacteroidetes (56.12%) was lower and that of phylum Firmicutes was higher (37.06%) in CHD patients than those in the controls (60.92% and 32.06%, P < 0.05). PCoA and UPGMA tree analysis showed that there were significant differences of gut microbial compositions between the two groups. Conclusion. The diversity and compositions of gut flora were different between CHD patients and healthy controls. The incidence of CHD might be associated with the alteration of gut microbiota.
The crosstalk between the gut microbiota and immune state of the host is an essential focus in academia and clinics. To explore the dynamic role of the microbiota in response to immune deficiency, we comprehensively assessed the microbiome of 90 mouse fecal samples, across three time points including two immunodeficiency models, namely severe combined immunodeficient (SCID) mice and non-obese diabetic SCID (NOD/SCID) mice, with BALB/cA as a control strain. Metagenomic analysis revealed a decrease in alpha diversity and the existence of a clear structural separation in the microbiota of immunodeficient mice. Although nuances exist between SCID and NOD/SCID mice, an increase in the protective microbiota, in particular Lactobacillus, contributed the most to the discrimination of immunodeficient and control mice. Further data regarding the red blood cell (RBC) concentration and serum IgA level during different stages of development support the concept of the microbiota alleviating the advancement of immune deficiency, which is called microbial compensation. Taken together, these results demonstrate the dynamic impact of immunodeficiency on the gut microbiota and the adaptive alteration of the microbiota that may influence the host state.
Human flora‐associated (HFA) piglet model was established to examine the effects of gut microbes from a different donor species on the intestinal morphology and mucosal immunity. Newborn germ‐free piglets, obtained by caesarean section, were orally inoculated with a human and a porcine faecal suspension, and artificially fed to establish a HFA group (n = 7) and pig flora‐associated (PFA) group (n = 7), respectively. All pigs were killed 6 weeks later. Tissue samples from duodenum, jejunum, ileum and colon were collected and studied by histochemistry and immunohistochemistry methods for intestinal morphological analyses and detection of immunocompetent cells. In summary, both groups of pigs performed well but HFA pigs had a somewhat better daily weight gain, and their jejunal villus height and crypt depth were significantly higher. In comparison with PFA pigs, the number of intraepithelial lymphocytes in jejunum was lower but the number of goblet cells containing neutral mucins was significantly increased in HFA pigs. No difference was observed in the number of mast cells. The areas of IgA producing cells and CD4+ T cells in the jejunum and IgG producing cells in the small intestine were significantly higher in HFA pigs. However, the areas of MHC class II expressing cells were significantly increased in the duodenum and colon. Additionally, the amount of Bifidobacteria spp. was significantly higher in HFA pigs. This study confirms that the composition of gut microbes differentially affects the host intestinal mucosal immunity and suggests that commensal bacteria have great effects on intestinal health and development.
Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro . This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.
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