38Literature regarding the differences in gut microbiota between exclusively breastfed (EBF) and 39 non-EBF infants is meager with large variation in methods and results. We performed a meta-40 analysis of seven studies (a total of 1825 stool samples from 684 infants) to investigate effects of 41 EBF compared to non-EBF on infant gut microbiota across different populations. In the first 6 42 months of life, overall bacterial diversity, gut microbiota age, relative abundances of 43 Bacteroidetes and Firmicutes and microbial-predicted pathways related to carbohydrate 44 metabolism were consistently increased; while relative abundances of pathways related to lipid, 45 3 vitamin metabolism and detoxification were decreased in non-EBF vs. EBF infants. The 46 perturbation in microbial-predicted pathways associated with non-EBF was larger in infants 47 delivered by C-section than delivered vaginally. Longer duration of EBF mitigated diarrhea-48 associated gut microbiota dysbiosis and the effects of EBF persisted after 6 months of age. These 49 consistent findings across vastly different populations suggest that one of the mechanisms of 50 short and long-term benefits of EBF may be alteration in gut microbes. 51 52 Background 55Establishment of the gut microbiota in early life has substantial impact on subsequent health 1 . 56Common sources of the infant's intestinal microorganisms are from the mother's skin, vagina, 57 stool and from breastfeeding 2-5 . There is a close relationship between the infant's gut microbiota 58 and the mother's breast milk microbiota and human milk oligosaccharides (HMO) composition 59 6-9 . Indeed, recent evidence has shown that breast milk microbiota can directly seed the infant 60 gut microbiota and the effects of breastmilk on infant gut microbiota is dose-dependent 5 . The 61 microbiota in breast milk changes over time during lactation and has been shown to be different 62 between exclusive breastfeeding (EBF) vs. non-EBF mothers 10,11 . Gut microbial abundances in 63 breast-fed infants, especially bifidobacterial species, are correlated with the mother's HMOs and 64 HMO-related catabolic activity 3,12,13 . Infant gut microbiota have been shown to be different 65 between breast fed vs. formula-fed infants 14-20 and change rapidly during the transition from 66 breastfeeding to formula 21 . 67 68 4 EBF in the first 6 months of life provides a multitude of health benefits 22,23 . For example, EBF 69has been shown to be strongly protective against diarrhea morbidity and mortality 24 and 70 decreases long-term risk of diabetes and obesity as compared to non-EBF or formula-fed infants 71 [25][26][27] . We hypothesize that the numerous benefits of EBF may be in part due to its effects on the 72 infant gut microbiota. Several recent studies have identified varying differences in gut microbial 73 composition or diversity between EBF and non-EBF infants 5,28-30 or gradients in the gut 74 microbiota composition or diversity across EBF, non-EBF and non-breastfed (non-BF) infants 75 5,14,29,31,32 . H...