Under homeostatic conditions (mora et al., 201), administration of a multi-strain probiotic preparation was associated with limited colonization in mice and with person-specific gut mucosal colonization resistance in humans. To study the post-antibiotic mucosal colonization capacity of probiotics and their impact on the indigenous mucosal microbiome as compared to aFMT or watchful waiting, we performed the MUcosal Search for Probiotic Impact and Colonization 3 (MUSPIC3) study in mice and in humans. In mice, we supplemented the drinking water of adult male wild-type (WT) C57BL/6 mice with a broad-spectrum antibiotic regimen of ciprofloxacin and metronidazole for 2 weeks. The immediate impact of antibiotic treatment on gut mucosal microbiome configuration was assessed in one group of mice sacrificed after the 2-week antibiotic exposure (Figure 1A, “Antibiotics”). The remaining animals (n = 30) were divided into three post-antibiotic intervention groups. In the first group (“Probiotics”), antibiotic treatment was followed by 4 weeks of daily administration by oral gavage of a commercially prescribed probiotics product involving 11 strains that was validated for composition and viability by multiple methods (mora et al., 201): Lactobacillus acidophilus (LAC), L. casei (LCA), L. casei sbsp. paracasei (LPA), L. plantarum (LPL), L. rhamnosus (LRH), Bifidobacterium longum (BLO), B. bifidum (BBI), B. breve (BBR), B. longum sbsp. infantis (BIN), Lactococcus lactis (LLA), and Streptococcus thermophilus (STH). Each mouse of the second group (“aFMT”) received, on the day following cessation of antibiotics, an oral gavage of its own pre-antibiotics stool microbiome. A third group (“Spontaneous”) remained untreated following antibiotic therapy to assess the spontaneous recovery of the indigenous gut microbiome in this setting. An additional group of mice (“Control”) did not receive antibiotics or any other treatment and was followed throughout the study’s duration.