Human milk oligosaccharides (HMOS) are not digested in the proximal intestine. In distal intestine, HMOS collectively modify the microbiota, but the response of individual bacteria to individual components of the HMOS is not well defined. Here, each of 25 major isolates of the human intestinal microbiota was fed individual major fucosylated and sialylated HMOS in anaerobic culture. This allowed for an assessment of the influence of specific HMOS on the growth and metabolic products of individual microbiota bacteria. Most Bifidobacteria spp. and Bacteroides spp. grew, induced α-L-fucosidase activity, and produced abundant lactate or short-chain fatty acids (SCFAs) when fed 2'-fucosyllactose (2'-FL), 3-FL, and lactodifucotetraose (LDFT). Lactobacillus delbrueckii ATCC7830, Enterococcus faecalis ATCC19433, and Streptococcus thermophilus ATCC19258 exhibited slight growth, pH reduction, and lactate production when supplemented with 2'-FL or 3-FL, but not LDFT. Supplementation with 3'-sialyllactose (3'-SL) and 6'-SL promoted moderate growth of Bifidobacterium longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, Bacteroides vulgatus ATCC8482, and B. thetaiotaomicron ATCC29148; accordingly, these bacteria exhibited greater neuraminidase activity and produced copious lactate, SCFA, or both. Lactobacillus delbrueckii ATCC7830 also consumed 6'-SL. In contrast, Clostridium spp., L. rhamnosus ATCC53103, E. faecalis ATCC29200, Staphylococcus spp., Enterobacter spp., and Escherichia coli K12 did not consume milk oligosaccharides nor produce appreciable acidic fermentation products. Specific Bifidobacteria and Bacteroides differentially digest specific individual HMOS, with the major fucosylated milk oligosaccharides most strongly stimulating key species of mutualist symbionts. This suggests strategies for treating dysbiosis of the microbiota and associated inflammatory disorders.
Breast-fed infant microbiota is typically rich in bifidobacteria. Herein, major human milk oligosaccharides (HMOS) are assessed for their ability to promote the growth of bifidobacteria and to acidify their environment, key features of prebiotics. During in vitro anaerobic fermentation of infant microbiota, supplementation by HMOS significantly decreased the pH even greater than supplementation by fructooligosaccharide (FOS), a prebiotic positive control. HMOS elevated lactate concentrations, increased the proportion of Bifidobacterium spp. in culture, and through their fermentation into organic acids, decreased the proportion of Escherichia and Clostridium perfringens. Three principal components of HMOS, 2'-fucosyllactose, lactodifucotetraose and 3-fucosyllactose, were consumed in these cultures. These three principal oligosaccharides of human milk were then individually tested as supplements for in vitro growth of four individual representative strains of infant gut microbes. Bifidobacterium longum JCM7007 and B. longum ATCC15697 efficiently consumed oligosaccharides and produced abundant lactate and short-chain fatty acids, resulting in significant pH reduction. The specificity of fermentation differed by microbe species and strain and by oligosaccharide structure. Escherichia coli K12 and C. perfringens did not utilize appreciable fucosylated oligosaccharides, and a typical mixture of organic acid fermentation products inhibited their growth. In summary, 2'-fucosyllactose, lactodifucotetraose, and 3-fucosyllactose, when cultured with B. longum JCM7007 and B. longum ATCC15697, exhibit key characteristics of a prebiotic in vitro. If these bifidobacteria are representative of pioneering or keystone species for human microbiota, fucosylated HMOS could strongly promote colonization and maintenance of a mutualist symbiotic microbiome. Thus, these simple glycans could mediate beneficial effects of human milk on infant health.
Defining the biologic roles of human milk oligosaccharides (HMOS) requires an efficient, simple, reliable, and robust analytical method for simultaneous quantification of oligosaccharide profiles from multiple samples. The HMOS fraction of milk is a complex mixture of polar, highly branched, isomeric structures that contain no intrinsic facile chromophore, making their resolution and quantification challenging. A liquid chromatography-mass spectrometry (LC-MS) method was devised to resolve and quantify 11 major neutral oligosaccharides of human milk simultaneously. Crude HMOS fractions are reduced, resolved by porous graphitic carbon HPLC with a water/acetonitrile gradient, detected by mass spectrometric specific ion monitoring, and quantified. The HPLC separates isomers of identical molecular weights allowing 11 peaks to be fully resolved and quantified by monitoring mass to charge (m/z) ratios of the deprotonated negative ions. The standard curves for each of the 11 oligosaccharides is linear from 0.078 or 0.156 to 20 μg/mL (R2 > 0.998). Precision (CV) ranges from 1% to 9%. Accuracy is from 86% to 104%. This analytical technique provides sensitive, precise, accurate quantification for each of the 11 milk oligosaccharides and allows measurement of differences in milk oligosaccharide patterns between individuals and at different stages of lactation.
The present study supports the observation that children with autism who have symptoms of gastrointestinal disorders have objective findings similar to children without autism. Neither noninvasive testing nor endoscopic findings identify gastrointestinal pathology specific to autism, but may be of benefit in identifying children with autism who have atypical symptoms.
Salmonella infection is more frequent among infants than the general population, but the incidence is lower in breastfed babies. This study was to test whether human milk per se inhibited salmonella invasion of human intestinal epithelial cells in vitro, and to identify the milk components likely to be responsible for any inhibition. Salmonella typhimurium SL1344 invasion of FHs 74 Int and CaCo‐2 cells were the models of human intestinal epithelium infection. Internalization of FITC‐labeled salmonella into intestinal cells was measured by FACS analysis to quantify infection. Pooled human milk and its fractions were tested for their ability to inhibit infection, including two human milk mucins, mucin 1 and mucin 4. At 150 ng/mL, approximating the amount in milk, human milk mucin 1 and mucin 4 inhibited salmonella invasion of both cell types. They also bound Salmonella typhimurium SL1344 in a dose‐dependent manner. Thus, mucins may prove useful as a basis for the development of novel oral prophylactic and therapeutic agents that inhibit infant diseases caused by salmonella, and perhaps other pathogens. Supported by NIH HD013021 and AI075563.
WHAT'S KNOWN ON THIS SUBJECT:The direct effects of prolactin on the nutritional and antimicrobial composition of breast milk have not been examined previously in women. WHAT THIS STUDY ADDS:The study demonstrates that recombinant human prolactin increases milk volume, induces changes in milk composition consistent with those during normal lactogenesis, and increases antimicrobially active oligosaccharide concentrations. The data suggest that prolactin is an important mediator of normal lactogenesis. abstract OBJECTIVE: The objective of this study was to determine the impact of recombinant human prolactin (r-hPRL) on the nutritional and immunologic composition of breast milk. METHODS:We conducted 2 trials of r-hPRL treatment. In the first study, mothers with documented prolactin deficiency were given r-hPRL every 12 hours in a 28-day, open-label trial. In the second study, mothers with lactation insufficiency that developed while they were pumping breast milk for their preterm infants were given r-hPRL daily in a 7-day, double-blind, placebo-controlled trial. Breast milk characteristics were compared before and during 7 days of treatment. RESULTS:Among subjects treated with r-hPRL (N ϭ 11), milk volumes (73 Ϯ 36 to 146 Ϯ 54 mL/day; P Ͻ .001) and milk lactose levels (155 Ϯ 15 to 184 Ϯ 8 mmol/L; P ϭ .01) increased, whereas milk sodium levels decreased (12.1 Ϯ 2.0 to 8.3 Ϯ 0.5 mmol/L; P ϭ .02). Milk calcium levels increased in subjects treated with r-hPRL twice daily (2.8 Ϯ 0.6 to 5.0 Ϯ 0.9 mmol/L; P ϭ .03). Total neutral (1.5 Ϯ 0.3 to 2.5 Ϯ 0.4 g/L; P ϭ .04) and acidic (33 Ϯ 4 to 60 Ϯ 6 mg/L; P ϭ .02) oligosaccharide levels increased in r-hPRL-treated subjects, whereas total daily milk immunoglobulin A secretionwas unchanged.CONCLUSIONS: r-hPRL treatment increased milk volume and induced changes in milk composition similar to those that occur during normal lactogenesis. r-hPRL also increased antimicrobially active oligosaccharide concentrations. These effects were achieved for women with both prolactin deficiency and lactation insufficiency.
sparse. B. longum fermentation products inhibited C. jejuni and E. coli. Thus, HMOS most strongly promoted growth of the two mutualists, and both HMOS and GMOS were efficiently fermented by these mutualists into organic acids. This is consistent with a primary role of HMOS in guiding early colonization of the infant microbiota by mutualist symbionts, and of plant oligosaccharides, especially GMOS, in maintaining a favorable microbiota through adulthood.Keywords Human milk oligosaccharides · Plant oligosaccharides · Microbiota · Prebiotic · Organic acids Abbreviations HMOSHuman milk oligosaccharides GMOS Gluco-manno-oligosaccha-Abstract Gut microbiota is important to human health. Specific dietary glycans promote favorable microbiota growth and inhibit pathobionts. Dietary glycans most relevant to adults and weaned infants are derived from plants or lactose; human milk oligosaccharides (HMOS) are most relevant to breastfed infants. Their efficacy in supporting bacterial growth is compared to determine their potential roles in the initiation and maintenance of colonization. Bioactivities of gluco-manno-oligosaccharides (GMOS), galacto-oligosaccharides (GOS), xylo-oligosaccharides (XOS), cellobiose (CBS), HMOS, and the most prominent individual HMOS, 2′-fucosyllactose (2′-FL) were contrasted. Two representative gut microbiota mutualists, Bifidobacteria longum ATCC15697 and Lactobacillus acidophilus NRRL B-4495, and two non-mutualists, Campylobacter jejuni S107 and Escherichia coli K12, were used to assess the in vitro prebiotic potential of these oligosaccharides. All oligosaccharides afforded growth of B. longum and L. acidophilus, with HMOS supporting the most robust growth, while none of these oligosaccharides afforded meaningful growth of non-mutualists. B. longum efficiently converted HMOS, GMOS, GOS, and XOS into organic acid fermentation products, and, to a lesser degree, L. acidophilus metabolized HMOS, GMOS, and GOS. Fermentation of these glycans by C. jejuni and E. coli was
A “safety-catch” linker strategy has been used to release a portion of the products of a Diels–Alder reaction conducted on a microelectrode array for characterization of stereochemistry. The attachment and cleavage of organic compounds from the surface of selected electrodes in the array can be accomplished by site-selective generation of base or acid at the electrode. It was found that the surface of the array had a minor influence on the stereochemistry of the Diels–Alder reaction, leading to slightly more of the exo-product relative to a similar solution-phase reaction.
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