The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.

Background Antibiotic-resistant (AR) bacteria are a global threat. AR bacteria can be acquired in early life and have long-term sequelae. Limiting the spread of antibiotic resistance without triggering the development of additional resistance mechanisms is of immense clinical value. Here, we show how the infant gut microbiome can be modified, resulting in a significant reduction of AR genes (ARGs) and the potentially pathogenic bacteria that harbor them. Methods The gut microbiome was characterized using shotgun metagenomics of fecal samples from two groups of healthy, term breastfed infants. One group was fed B. infantis EVC001 in addition to receiving lactation support ( n = 29, EVC001-fed), while the other received lactation support alone ( n = 31, controls). Coliforms were isolated from fecal samples and genome sequenced, as well as tested for minimal inhibitory concentrations against clinically relevant antibiotics. Results Infants fed B. infantis EVC001 exhibited a change to the gut microbiome, resulting in a 90% lower level of ARGs compared to controls. ARGs that differed significantly between groups were predicted to confer resistance to beta lactams, fluoroquinolones, or multiple drug classes, the majority of which belonged to Escherichia , Clostridium, and Staphylococcus . Minimal inhibitory concentration assays confirmed the resistance phenotypes among isolates with these genes. Notably, we found extended-spectrum beta lactamases among healthy, vaginally delivered breastfed infants who had never been exposed to antibiotics. Conclusions Colonization of the gut of breastfed infants by a single strain of B. longum subsp. infantis had a profound impact on the fecal metagenome, including a reduction in ARGs. This highlights the importance of developing novel approaches to limit the spread of these genes among clinically relevant bacteria. Future studies are needed to determine whether colonization with B. infantis EVC001 decreases the incidence of AR infections in breastfed infants. Trial registration This clinical trial was registered at ClinicalTrials.gov , NCT02457338. Electronic supplementary material The online version of this article (10.1186/s13756-019-0583-6) contains supplementary material, which is available to authorized users.

Objectives Several seminal publications identify that Bifidobacterium longum subsp. infantis (B. infantis) has uniquely evolved to be the predominant strain in the breastfed infant gut; however, recent cohort studies indicate it is now far less abundant in infants born in industrialized nations, along with increased abundance of potentially pathogenic bacteria and gut dysbiosis. Importantly, recent clinical studies show enteric dysbiosis during the first 100 days of life can lead to higher risk of allergic and autoimmune-mediated disorders later in life. Given the importance of the microbiome for immune system development, we investigated the effect of B. infantis EVC001 consumption on intestinal inflammation in a cohort of healthy, term infants. Methods Forty (n = 40) infants were randomly selected from the previously conducted clinical study in which healthy, exclusively breastfed infants were either fed B. infantis EVC001 daily for 21 days, starting at day 7 postpartum, or received breastmilk alone. Stool samples were collected at multiple times postnatally and analyzed for cytokine production using a multiplex system and calprotectin ELISA. Results Baseline analysis indicated infants randomized to the EVC001 group produced naturally higher levels of IL2, IL5, IL6, IL10, TNFa and IFNg and lower levels of IL1b (all P < 0.01); however, by day 40, infants fed EVC001 produced significantly decreased cytokines, IL1b, IL6, IL8, IL22, TNFa and IFNg (all P < 0.0001) and IL-5 (P = 0.024), and at day 60 postpartum (all P < 0.001) and IL5 (P = 0.013). Fecal calprotectin concentration was significantly decreased in infants whose gut microbiome contained Bifidobacterium (P = 9.61e-05). Conclusions This study is the first to demonstrate a significant impact of B. infantis EVC001 on immune homeostasis in breastfed infants during a critical window of immune system development. Infants fed EVC001 produced significantly less proinflammatory cytokines and fecal calprotectin compared to control infants. Notably, TNFa, IL1b, and IFNg, which increase intestinal permeability, were significantly elevated in control infants. This may play an important mechanistic role in explaining the chronic intestinal inflammation observed in infants not colonized with B. infantis. These critical data provide a new understanding of the role of the infant gut microbiome in immune system development and provide novel applications to address chronic inflammation through modulation of gut dysbiosis. Funding Sources Industry funded.

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