Dataset Information

Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas.

ABSTRACT:

Background

Akkermansia muciniphila is one of the most dominant bacteria that resides on the mucus layer of intestinal tract and plays key role in human health, however, little is known about its genomic content.

Results

Herein, we for the first time characterized the genomic architecture of A. muciniphila based on whole-genome sequencing, assembling, and annotating of 39 isolates derived from human and mouse feces. We revealed a flexible open pangenome of A. muciniphila currently consisting of 5644 unique proteins. Phylogenetic analysis identified three species-level A. muciniphila phylogroups exhibiting distinct metabolic and functional features. Based on the comprehensive genome catalogue, we reconstructed 106 newly A. muciniphila metagenome assembled genomes (MAGs) from available metagenomic datasets of human, mouse and pig gut microbiomes, revealing a transcontinental distribution of A. muciniphila phylogroups across mammalian gut microbiotas. Accurate quantitative analysis of A. muciniphila phylogroups in human subjects further demonstrated its strong correlation with body mass index and anti-diabetic drug usage. Furthermore, we found that, during their mammalian gut evolution history, A. muciniphila acquired extra genes, especially antibiotic resistance genes, from symbiotic microbes via recent lateral gene transfer.

Conclusions

The genome repertoire of A. muciniphila provided insights into population structure, evolutionary and functional specificity of this significant bacterium.

SUBMITTER: Guo X

PROVIDER: S-EPMC5648452 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The mucophilic anaerobic bacterium Akkermansia muciniphila is a prominent member of the gastrointestinal (GI) microbiota and the only known species of the Verrucomicrobia phylum in the mammalian gut. A high prevalence of A. muciniphila in adult humans is associated with leanness and a lower risk for the development of obesity and diabetes. Four distinct A. muciniphila phylogenetic groups have been described, but little is known about their relative abundance in humans or how they impact human metabolic health. In this study, we isolated and characterized 71 new A. muciniphila strains from a cohort of children and adolescents undergoing treatment for obesity. Based on genomic and phenotypic analysis of these strains, we found several phylogroup-specific phenotypes that may impact the colonization of the GI tract or modulate host functions, such as oxygen tolerance, adherence to epithelial cells, iron and sulfur metabolism, and bacterial aggregation. In antibiotic-treated mice, phylogroups AmIV and AmII outcompeted AmI strains. In children and adolescents, AmI strains were most prominent, but we observed high variance in A. muciniphila abundance and single phylogroup dominance, with phylogroup switching occurring in a small subset of patients. Overall, these results highlight that the ecological principles determining which A. muciniphila phylogroup predominates in humans are complex and that A. muciniphila strain genetic and phenotypic diversity may represent an important variable that should be taken into account when making inferences as to this microbe's impact on its host's health.IMPORTANCE The abundance of Akkermansia muciniphila in the gastrointestinal (GI) tract is linked to multiple positive health outcomes. There are four known A. muciniphila phylogroups, yet the prevalence of these phylogroups and how they vary in their ability to influence human health is largely unknown. In this study, we performed a genomic and phenotypic analysis of 71 A. muciniphila strains and identified phylogroup-specific traits such as oxygen tolerance, adherence, and sulfur acquisition that likely influence colonization of the GI tract and differentially impact metabolic and immunological health. In humans, we observed that single Akkermansia phylogroups predominate at a given time but that the phylotype can switch in an individual. This collection of strains provides the foundation for the functional characterization of A. muciniphila phylogroup-specific effects on the multitude of host outcomes associated with Akkermansia colonization, including protection from obesity, diabetes, colitis, and neurological diseases, as well as enhanced responses to cancer immunotherapies.

Project description:Excessive mucin degradation by intestinal bacteria may contribute to inflammatory bowel diseases because access of luminal antigens to the intestinal immune system is facilitated. This study investigated how the presence of a mucin degrading commensal bacterium affects the severity of an intestinal Salmonella enterica Typhimurium-induced gut inflammation. Using a gnotobiotic C3H mouse model with a background microbiota of eight bacterial species (SIHUMI) the impact of the mucin-degrading commensal bacterium Akkermansia muciniphila (SIHUMI-A) on inflammatory and infectious symptoms caused by S. Typhimurium was investigated. Presence of A. muciniphila in S. Typhimurium-infected SIHUMI mice caused significantly increased histopathology scores and elevated mRNA levels of IFN-?, IP-10, TNF-?, IL-12, IL-17 and IL-6 in cecal and colonic tissue. The increase in pro-inflammatory cytokines was accompanied by 10-fold higher S. Typhimurium cell numbers in mesenteric lymph nodes of SIHUMI mice associated with A. muciniphila and S. Typhimurium (SIHUMI-AS) compared to SIHUMI mice with S. Typhimurium only (SIHUMI-S). The number of mucin filled goblet cells was 2- to 3-fold lower in cecal tissue of SIHUMI-AS mice compared to SIHUMI-S, SIHUMI-A or SIHUMI mice. Reduced goblet cell numbers significantly correlated with increased IFN-? mRNA levels (r(2)?=?-0.86, ***P<0.001) in all infected mice. In addition, loss of cecal mucin sulphation was observed in SIHUMI mice containing both A. muciniphila and S. Typhimurium compared to other mouse groups. Concomitant presence of A. muciniphila and S. Typhimurium resulted in a drastic change in microbiota composition of SIHUMI mice: the proportion of B. thetaiotaomicron in SIHUMI-AS mice was 0.02% of total bacteria compared to 78%-88% in the other mouse groups and the proportion of S. Typhimurium was 94% in SIHUMI-AS mice but only 2.2% in the SIHUMI-S mice. These results indicate that A. muciniphila exacerbates S. Typhimurium-induced intestinal inflammation by its ability to disturb host mucus homeostasis.

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Project description:The objective of this study was to elucidate the effect of intestinal Akkermansia muciniphila bacteria on fatty liver disease. Five-week-old C57BL/6N mice were administered either phosphate-buffered saline (PBS; control) or A. muciniphila at 108 to 109 CFU/ml, and were fed either a 45% fat diet (high-fat diet [HFD]) or a 10% fat diet (normal diet [ND]) for 10 weeks. After 10 weeks, the mice were euthanized, and blood and tissue samples, including adipose tissue, cecum, liver, and brain, were immediately collected. Biochemical and histological analyses were conducted, and the expression levels of related factors were compared to determine the antiobesity effects of Akkermansia muciniphila The gut microbiome was analyzed in fecal samples. Oral administration of A. muciniphila significantly (P?<?0.05) lowered serum triglyceride (TG) and alanine aminotransferase (ALT) levels in obese mice. Compared to the non-A. muciniphila-treated group, the expression of SREBP (regulator of TG synthesis in liver tissue) was decreased in the A. muciniphila-treated group. The expression of IL-6 in the liver of obese mice was decreased following the administration of A. muciniphila Furthermore, alterations in the ratio of Firmicutes to Bacteroidetes and the decrease in bacterial diversity caused by the HFD were restored upon the administration of A. muciniphila These results indicate that A. muciniphila prevents fatty liver disease in obese mice by regulating TG synthesis in the liver and maintaining gut homeostasis.IMPORTANCE This study investigated the effect of Akkermansia muciniphila on fatty liver disease. Although some research about the effects of A. muciniphila on host health has been published, study of the relationship between A. muciniphila administration and fatty liver, as well as changes in the gut microbiota, has not been conducted. In this study, we demonstrated that A. muciniphila prevented fatty liver disease by regulation of the expression of genes that regulate fat synthesis and inflammation in the liver.