The study of the extreme limits of human lifespan may allow a better understanding
of how human beings can escape, delay, or survive the most frequent age-related causes
of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex
trait in which genetics, environment, and stochasticity concur to determine the chance
to reach 100 or more years of age [1]. Because of its impact on human metabolism and
immunology, the gut microbiome has been proposed as a possible determinant of healthy
aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract
inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health
[6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota
and a long-living host, we provide for the first time the phylogenetic microbiota
analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults,
elderly, and centenarians, thus reconstructing the longest available human microbiota
trajectory along aging. We highlighted the presence of a core microbiota of highly
occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae,
Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing
along with age. Aging is characterized by an increasing abundance of subdominant species,
as well as a rearrangement in their co-occurrence network. These features are maintained
in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians,
describing changes that, even accommodating opportunistic and allochthonous bacteria,
might possibly support health maintenance during aging, such as an enrichment and/or
higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium,
and Christensenellaceae).