Populations with obesity and Type 2 Diabetes differ from healthy populations in the abundance of certain gut microbial species and microbial gene richness (MGR). Abundance of Akkermansia muciniphila (Akk) has been inversely associated to fat mass and glucose intolerance in mice. More evidence is needed in humans as well as on the impact of diet and weight loss on Akk abundance. Our aim was to evaluate the association between fecal Akk abundance and MGR, host characteristics, and their changes as a result of calorie restriction (CR) for 6 weeks followed by weight stabilization (WS) for 6 weeks in 49 overweight/obese adults. Fecal Akk, MGR, diet and bioclinical parameters were measured at baseline (BS) and after CR and WS. At BS Akk was inversely related to fasting glucose, waist-to-hip ratio, and adipocyte diameter in subcutaneous white adipose tissue. Subjects with higher MGR and Akk had the healthiest metabolic status, particularly in fasting glucose, triglycerides and body composition. Higher BS Akk was associated with greater improvement in insulin sensitivity and other clinical parameters after CR. Akk is associated with a healthier metabolic status and outcomes after CR in this population. Further studies are required to establish underlying mechanisms in humans. Support: ANR MICRO-Obes, KOT-Ceprodi, Fondation Coeur et Arteres, Metacardis HEALTH-F4-2012-305312, FRS-FNRS, ERC Starting grant 336452-ENIGMO).