Background and aims: Many forms of immune dysregulation, which lead to inflammaging and senescence, have been demonstrated in patients with systemic lupus erythematosus (SLE; lupus) and in the aging population. The discovery of the microbiome and its association with human health and pathology has led it to be the center of investigation as a major contributor to the pathogenesis of immunosenescence in both populations. Similar alterations to the microbiome in the form of dysbiosis, that are demonstrated in both aging and in lupus patients, may help explain the significant overlap in clinical manifestations seen in these groups. Methods: We performed an extensive literature review, utilizing the Pubmed search engine and Google Scholar for studies evaluating the microbiome in two groups, elderly populations and lupus patients (both murine and human models), between the years 2000–2019. We searched for the terms: microbiome, dysbiosis, lupus, elderly, aging and inflammaging, which yielded hundreds of articles, of which 114 were used for preparation of this paper. We compared the similarities between the populations. Results: We found that the similar processes of immune dysregulation, in both aging populations and lupus patients, extend to the microbiome, in the form of dysbiosis. Some of these similarities include loss of microbiota biodiversity, increased representation of microbes that are associated with inflammation and disease (i.e Proteobacteria, Bacteroidetes), a relative decrease in protective microbes with “anti-inflammatory” properties (i.e Firmicutes) and a subsequent compromise to the intestinal barrier, leading to leakage of proinflammatory microbial components in both groups. Conclusions: We conclude that there are several similar alterations in the composition and function of the microbiome of lupus patients and aging individuals, leading to immunosenescence, which may also be a contributing mechanism in lupus. It seems in fact that the microbiome of SLE may actually be analogous to immunosenescence. This knowledge may help the continuous efforts in finding a solution for both conditions.