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      Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of Bifidobacterium over the Past Century

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          Abstract

          Historically, Bifidobacterium species were reported as abundant in the breastfed infant gut. However, recent studies in resource-rich countries show an increased abundance of taxa regarded as signatures of dysbiosis.

          ABSTRACT

          Historically, Bifidobacterium species were reported as abundant in the breastfed infant gut. However, recent studies in resource-rich countries show an increased abundance of taxa regarded as signatures of dysbiosis. It is unclear whether these differences are the product of genetics, geographic factors, or interventions such as formula feeding, antibiotics, and caesarean section. Fecal pH is strongly associated with Bifidobacterium abundance; thus, pH could be an indicator of its historical abundance. A review of 14 clinical studies published between 1926 and 2017, representing more than 312 healthy breastfed infants, demonstrated a change in fecal pH from 5.0 to 6.5 (adjusted r 2 = 0.61). This trend of increasing infant fecal pH over the past century is consistent with current reported discrepancies in Bifidobacterium species abundance in the gut microbiome in resource-rich countries compared to that in historical reports. Our analysis showed that increased fecal pH and abundance of members of the families Enterobacteriaceae, Clostridiaceae, Peptostreptococcaceae, and Veillonellaceae are associated, indicating that loss of highly specialized Bifidobacterium species may result in dysbiosis, the implications of which are not yet fully elucidated. Critical assessment of interventions that restore this ecosystem, measured by key parameters such as ecosystem productivity, gut function, and long-term health, are necessary to understand the magnitude of this change in human biology over the past century.

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          Most cited references26

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          Human milk glycobiome and its impact on the infant gastrointestinal microbiota.

          Human milk contains an unexpected abundance and diversity of complex oligosaccharides apparently indigestible by the developing infant and instead targeted to its cognate gastrointestinal microbiota. Recent advances in mass spectrometry-based tools have provided a view of the oligosaccharide structures produced in milk across stages of lactation and among human mothers. One postulated function for these oligosaccharides is to enrich a specific "healthy" microbiota containing bifidobacteria, a genus commonly observed in the feces of breast-fed infants. Isolated culture studies indeed show selective growth of infant-borne bifidobacteria on milk oligosaccharides or core components therein. Parallel glycoprofiling documented that numerous Bifidobacterium longum subsp. infantis strains preferentially consume small mass oligosaccharides that are abundant early in the lactation cycle. Genome sequencing of numerous B. longum subsp. infantis strains shows a bias toward genes required to use mammalian-derived carbohydrates by comparison with adult-borne bifidobacteria. This intriguing strategy of mammalian lactation to selectively nourish genetically compatible bacteria in infants with a complex array of free oligosaccharides serves as a model of how to influence the human supraorganismal system, which includes the gastrointestinal microbiota.
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            The role of the intestinal microbiota in type 1 diabetes mellitus.

            Type 1 diabetes mellitus (T1DM) is a chronic immune-mediated disease with a subclinical prodromal period, characterized by selective loss of insulin-producing-β cells in the pancreatic islets of genetically susceptible individuals. The incidence of T1DM has increased several fold in most developed countries since World War II, in conjunction with other immune-mediated diseases. Rapid environmental changes and modern lifestyles are probably the driving factors that underlie this increase. These effects might be mediated by changes in the human microbiota, particularly the intestinal microbiota. Research on the gut microbiome of individuals at risk of developing T1DM and in patients with established disease is still in its infancy, but initial findings indicate that the intestinal microbiome of individuals with prediabetes or diabetes mellitus is different to that of healthy individuals. The gut microbiota in individuals with preclinical T1DM is characterized by Bacteroidetes dominating at the phylum level, a dearth of butyrate-producing bacteria, reduced bacterial and functional diversity and low community stability. However, these changes seem to emerge after the appearance of autoantibodies that are predictive of T1DM, which suggests that the intestinal microbiota might be involved in the progression from β-cell autoimmunity to clinical disease rather than in the initiation of the disease process.
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              Stool microbiota and vaccine responses of infants.

              Oral vaccine efficacy is low in less-developed countries, perhaps due to intestinal dysbiosis. This study determined if stool microbiota composition predicted infant oral and parenteral vaccine responses. The stool microbiota of 48 Bangladeshi infants was characterized at 6, 11, and 15 weeks of age by amplification and sequencing of the 16S ribosomal RNA gene V4 region and by Bifidobacterium-specific, quantitative polymerase chain reaction. Responses to oral polio virus (OPV), bacille Calmette-Guérin (BCG), tetanus toxoid (TT), and hepatitis B virus vaccines were measured at 15 weeks by using vaccine-specific T-cell proliferation for all vaccines, the delayed-type hypersensitivity skin-test response for BCG, and immunoglobulin G responses using the antibody in lymphocyte supernatant method for OPV, TT, and hepatitis B virus. Thymic index (TI) was measured by ultrasound. Actinobacteria (predominantly Bifidobacterium longum subspecies infantis) dominated the stool microbiota, with Proteobacteria and Bacteroidetes increasing by 15 weeks. Actinobacteria abundance was positively associated with T-cell responses to BCG, OPV, and TT; with the delayed-type hypersensitivity response; with immunoglobulin G responses; and with TI. B longum subspecies infantis correlated positively with TI and several vaccine responses. Bacterial diversity and abundance of Enterobacteriales, Pseudomonadales, and Clostridiales were associated with neutrophilia and lower vaccine responses. Bifidobacterium predominance may enhance thymic development and responses to both oral and parenteral vaccines early in infancy, whereas deviation from this pattern, resulting in greater bacterial diversity, may cause systemic inflammation (neutrophilia) and lower vaccine responses. Vaccine responsiveness may be improved by promoting intestinal bifidobacteria and minimizing dysbiosis early in infancy. Copyright © 2014 by the American Academy of Pediatrics.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                mSphere
                mSphere
                msph
                msph
                mSphere
                mSphere
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2379-5042
                7 March 2018
                Mar-Apr 2018
                : 3
                : 2
                : e00041-18
                Affiliations
                [a ]Evolve BioSystems, Inc., Davis, California, USA
                [b ]Foods for Health Institute, University of California, Davis, California, USA
                [c ]Department of Pediatrics, UC Davis Children’s Hospital, Sacramento, California, USA
                [d ]Department of Food Science and Technology, University of California, Davis, California, USA
                [e ]Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, USA
                The Jackson Laboratory for Genomic Medicine
                Author notes
                Address correspondence to Jennifer T. Smilowitz, jensm@ 123456ucdavis.edu .

                Citation Henrick BM, Hutton AA, Palumbo MC, Casaburi G, Mitchell RD, Underwood MA, Smilowitz JT, Frese SA. 2018. Elevated fecal pH indicates a profound change in the breastfed infant gut microbiome due to reduction of Bifidobacterium over the past century. mSphere 3:e00041-18. https://doi.org/10.1128/mSphere.00041-18.

                Author information
                https://orcid.org/0000-0003-2053-5830
                Article
                mSphere00041-18
                10.1128/mSphere.00041-18
                5853487
                29564397
                e0c64435-e781-4377-8527-a84df89489a7
                Copyright © 2018 Henrick et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 18 January 2018
                : 12 February 2018
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 33, Pages: 6, Words: 3092
                Categories
                Observation
                Host-Microbe Biology
                Custom metadata
                March/April 2018

                bifidobacterium,biochemistry,infant microbiome,microbiome

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