Several studies suggest that microbial alterations (dysbiosis) are intimately linked to chronic inflammation occurring upon aging. The aim of this study was to investigate the potential interest of a synbiotic approach (co-administration of a probiotic bacteria and a prebiotic dietary fibre) to improve gastrointestinal wellness and inflammatory markers in middle-aged people. Middle-aged subjects were randomized to take synbiotic (Bifidobacterium animalis lactis and fructo-oligosaccharides (FOS)) or placebo for 30 days. Stool frequency and consistency were improved in both placebo and synbiotic-treated volunteers while the synbiotic treatment significantly decreased the number of days with abdominal discomfort. Synbiotic treatment had no impact on mood dimensions, quality of life scores or the overall composition of the gut microbiota (16S rRNA gene sequencing of DNA extracted from stool). Importantly, plasma proinflammatory cytokines (interleukin (IL)-6, IL-8, IL-17a and interferon-gamma (IFNγ)) were significantly lower after 30 days of synbiotic supplementation. This effect appears to be independent of the gut barrier function. This study demonstrates that a combination of B. animalis lactis and the well-known prebiotic FOS could be a promising synbiotic strategy to decrease inflammatory status with improvement of gut disorders in middle-aged people.