BackgroundInflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes.MethodsWe performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn.ResultsWe found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut.ConclusionsThis study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0490-5) contains supplementary material, which is available to authorized users.

Although survival to old age is known to have strong environmental and behavioral components, mortality differences between social groups tend to diminish or even disappear at older ages. Hypothesizing that surviving to extreme old age entails a substantial familial predisposition for longevity, we analyzed the pedigrees of 444 centenarian families in the United States. These pedigrees included 2,092 siblings of centenarians, whose survival was compared with 1900 birth cohort survival data from the U.S. Social Security Administration. Siblings of centenarians experienced a mortality advantage throughout their lives relative to the U.S. 1900 cohort. Female siblings had death rates at all ages about one-half the national level; male siblings had a similar advantage at most ages, although diminished somewhat during adolescence and young adulthood. Relative survival probabilities for these siblings increase markedly at older ages, reflecting the cumulative effect of their mortality advantage throughout life. Compared with the U.S. 1900 cohort, male siblings of centenarians were at least 17 times as likely to attain age 100 themselves, while female siblings were at least 8 times as likely.genetics ͉ aging ͉ longevity ͉ sibling pair ͉ oldest old M any centenarians live the majority of their exceptionally long lives in good health, demonstrating a rapid decline only near the end of life (1). Deciphering why centenarians markedly delay or in some cases even escape age-associated diseases could help in better understanding the pathogenesis of diseases such as stroke, heart disease, cancer, and Alzheimer's dementia, and the relative contributions of environment, behavior, and genetics in determining rates of aging and susceptibility or resistance to diseases that cause premature mortality (2).Whereas survival to old age is known to have a strong environmental and behavioral component, mortality differences between social groups tend to diminish or even disappear at older ages (3-5). One explanation for this phenomenon is that genetic factors unrelated to social groupings play a predominant role in survival chances at older ages. If genetic factors are indeed an important component of longevity, there should be greater similarity of individual longevity within families or lineages than within the population as a whole. We have documented the familial component of longevity in a variety of ways, as part of a larger study of centenarians in the United States.In a previous study, four families, impressive for the number of individuals achieving extreme old age, were identified (6). The question was explored as to whether such intrafamilial clustering could be attributed to chance alone, or if shared characteristics might be responsible for a collective ability to achieve extreme old age. A mathematical analysis was performed to determine the probability of families such as these occurring by random variation alone. Such probabilities were found to be extremely small (less than 1 per all of the families that exist in the world...