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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Formula-fed (FF) infants exhibit a different metabolic profile than breast-fed (BF) infants. Two potential mechanisms are the higher protein level in formula compared with breast milk and the removal of the milk fat and associated milk fat globule membranes (MFGM) during production of infant formula. To determine whether MFGM may impact metabolism, formula-fed infants were randomly assigned to receive either an MFGM isolate-supplemented experimental formula (EF) or a standard formula (SF) from 2 until 6 months and compared with a BF reference group. Infants consuming EF had higher levels of fatty acid oxidation products compared to infants consuming SF. Although the protein level in the study formula was approximately 12 g/L (lower than most commercial formulas), a metabolic difference between FF and BF remained such that FF infants had higher levels of amino acid catabolism by-products and a low efficiency of amino acid clearance (preference for protein metabolism). BF infants had higher levels of fatty acid oxidation products (preference for fat metabolism). These unique, energy substrate-driven metabolic outcomes did not persist after diet was shifted to weaning foods and appeared to be disrupted by complementary feeding. Our results suggest that MFGM may have a role in directing infant metabolism.

Human milk delivers an array of bioactive components that safeguard infant growth and development and maintain healthy gut microbiota. Milk fat globule membrane (MFGM) is a biologically functional fraction of milk increasingly linked to beneficial outcomes in infants through protection from pathogens, modulation of the immune system and improved neurodevelopment. In the present study, we characterized the fecal microbiome and metabolome of infants fed a bovine MFGM supplemented experimental formula (EF) and compared to infants fed standard formula (SF) and a breast-fed reference group. The impact of MFGM on the fecal microbiome was moderate; however, the fecal metabolome of EF-fed infants showed a significant reduction of several metabolites including lactate, succinate, amino acids and their derivatives from that of infants fed SF. Introduction of weaning food with either human milk or infant formula reduces the distinct characteristics of breast-fed- or formula-fed- like infant fecal microbiome and metabolome profiles. Our findings support the hypothesis that higher levels of protein in infant formula and the lack of human milk oligosaccharides promote a shift toward amino acid fermentation in the gut. MFGM may play a role in shaping gut microbial activity and function.

Background: Compared to breast-fed (BF), formula-fed (FF) infants exhibit more rapid weight gain, a different fecal microbial profile, as well as elevated serum insulin, insulin growth factor 1 (IGF-1), and branched chain amino acids (BCAAs). Since infant formula contains more protein and lower free amino acids than breast milk, it is thought that protein and/or free amino acids may be key factors that explain phenotypic differences between BF and FF infants. Methods: Newborn rhesus monkeys (Macaca mulatta) were either exclusively BF or fed regular formula or reduced protein formula either supplemented or not with a mixture of amino acids. Longitudinal sampling and clinical evaluation were performed from birth to 16 weeks including anthropometric measurements, intake records, collection of blood for hematology, serum biochemistry, hormones, and metabolic profiling, collection of urine for metabolic profiling, and collection of feces for 16s rRNA fecal microbial community profiling. Results: Reducing protein in infant formula profoundly suppressed intake, lowered weight gain and improved the FF-specific metabolic phenotype in the first month of age. This time-dependent change paralleled an improvement in serum insulin. All lower protein FF groups showed reduced protein catabolism with lower levels of blood urea nitrogen (BUN), urea, ammonia, albumin, creatinine, as well as lower excretion of creatinine in urine compared to infants fed regular formula. Levels of fecal microbes (Bifidobacterium and Ruminococcus from the Ruminococcaceae family), that are known to have varying ability to utilize complex carbohydrates, also increased with protein reduction. Adding free amino acids to infant formula did not alter milk intake or fecal microbial composition, but did significantly increase urinary excretion of amino acids and nitrogen-containing metabolites. However, despite the lower protein intake, these infants still exhibited a distinct FF-specific metabolic phenotype cha

Formula-fed (FF) infants exhibit a different metabolic profile than breast-fed (BF) infants. Two potential mechanisms are the higher protein level in formula compared with breast milk and the removal of the milk fat and associated milk fat globule membranes (MFGM) during production of infant formula. To determine whether MFGM may impact metabolism, formula-fed infants were randomly assigned to receive either an MFGM isolate-supplemented experimental formula (EF) or a standard formula (SF) from 2 until 6 months and compared with a BF reference group. Infants consuming EF had higher levels of fatty acid oxidation products compared to infants consuming SF. Although the protein level in the study formula was approximately 12 g/L (lower than most commercial formulas), a metabolic difference between FF and BF remained such that FF infants had higher levels of amino acid catabolism by-products and a low efficiency of amino acid clearance (preference for protein metabolism). BF infants had higher levels of fatty acid oxidation products (preference for fat metabolism). These unique, energy substrate-driven metabolic outcomes did not persist after diet was shifted to weaning foods and appeared to be disrupted by complementary feeding. Our results suggest that MFGM may have a role in directing infant metabolism.

Human milk delivers an array of bioactive components that safeguard infant growth and development and maintain healthy gut microbiota. Milk fat globule membrane (MFGM) is a biologically functional fraction of milk increasingly linked to beneficial outcomes in infants through protection from pathogens, modulation of the immune system and improved neurodevelopment. In the present study, we characterized the fecal microbiome and metabolome of infants fed a bovine MFGM supplemented experimental formula (EF) and compared to infants fed standard formula (SF) and a breast-fed reference group. The impact of MFGM on the fecal microbiome was moderate; however, the fecal metabolome of EF-fed infants showed a significant reduction of several metabolites including lactate, succinate, amino acids and their derivatives from that of infants fed SF. Introduction of weaning food with either human milk or infant formula reduces the distinct characteristics of breast-fed- or formula-fed- like infant fecal microbiome and metabolome profiles. Our findings support the hypothesis that higher levels of protein in infant formula and the lack of human milk oligosaccharides promote a shift toward amino acid fermentation in the gut. MFGM may play a role in shaping gut microbial activity and function.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Compared to breast-fed (BF), formula-fed (FF) infants exhibit more rapid weight gain, a different fecal microbial profile, as well as elevated serum insulin, insulin growth factor 1 (IGF-1), and branched chain amino acids (BCAAs). Since infant formula contains more protein and lower free amino acids than breast milk, it is thought that protein and/or free amino acids may be key factors that explain phenotypic differences between BF and FF infants. Methods: Newborn rhesus monkeys (Macaca mulatta) were either exclusively BF or fed regular formula or reduced protein formula either supplemented or not with a mixture of amino acids. Longitudinal sampling and clinical evaluation were performed from birth to 16 weeks including anthropometric measurements, intake records, collection of blood for hematology, serum biochemistry, hormones, and metabolic profiling, collection of urine for metabolic profiling, and collection of feces for 16s rRNA fecal microbial community profiling. Results: Reducing protein in infant formula profoundly suppressed intake, lowered weight gain and improved the FF-specific metabolic phenotype in the first month of age. This time-dependent change paralleled an improvement in serum insulin. All lower protein FF groups showed reduced protein catabolism with lower levels of blood urea nitrogen (BUN), urea, ammonia, albumin, creatinine, as well as lower excretion of creatinine in urine compared to infants fed regular formula. Levels of fecal microbes (Bifidobacterium and Ruminococcus from the Ruminococcaceae family), that are known to have varying ability to utilize complex carbohydrates, also increased with protein reduction. Adding free amino acids to infant formula did not alter milk intake or fecal microbial composition, but did significantly increase urinary excretion of amino acids and nitrogen-containing metabolites. However, despite the lower protein intake, these infants still exhibited a distinct FF-specific metabolic phenotype cha

To investigate the impact of probiotic supplementation of infant formula on immune parameters, intestinal microbiota, and metabolism, five individually housed infant rhesus monkeys exclusively fed standard infant formula supplemented with probiotics (Bifidobacterium animalis subsp. lactis HN019) from birth until 3 months of age were compared with five standard formula-fed and five breast-fed monkeys. Anthropometric measurements, serum insulin, immune parameters, fecal microbiota, and metabolic profiles of serum, urine, and feces were evaluated. Consumption of B. lactis-supplemented formula reduced microbial diversity, restructured the fecal microbial community, and altered the fecal metabolome at the last two time points, in addition to increasing short-chain fatty acids in serum and urine. Circulating CCL22 was lower and threonine, branched-chain amino acids, urea, and allantoin, as well as dimethylglycine in serum and urine, were increased in the group supplemented with B. lactis compared with the standard formula-fed group. These results support a role of probiotics as effectors of gut microbial activity regulating amino acid utilization and nitrogen cycling. Future risk-benefit analyses are still needed to consolidate the existing knowledge on the long-term consequences of probiotic administration during infancy. IMPORTANCE Probiotics are becoming increasingly popular due to their perceived effects on health, despite a lack of mechanistic information on how they impart these benefits. Infant formula and complementary foods are common targets for supplementation with probiotics. However, different probiotic strains have different properties, and there is a lack of data on long-term health effects on the consumer. Given the increasing interest in supplementation with probiotics and the fact that the gastrointestinal tracts of infants are still immature, we sought to determine whether consumption of infant formula containing the probiotic Bifidobacte

To investigate the impact of probiotic supplementation of infant formula on immune parameters, intestinal microbiota, and metabolism, five individually housed infant rhesus monkeys exclusively fed standard infant formula supplemented with probiotics (Bifidobacterium animalis subsp. lactis HN019) from birth until 3 months of age were compared with five standard formula-fed and five breast-fed monkeys. Anthropometric measurements, serum insulin, immune parameters, fecal microbiota, and metabolic profiles of serum, urine, and feces were evaluated. Consumption of B. lactis-supplemented formula reduced microbial diversity, restructured the fecal microbial community, and altered the fecal metabolome at the last two time points, in addition to increasing short-chain fatty acids in serum and urine. Circulating CCL22 was lower and threonine, branched-chain amino acids, urea, and allantoin, as well as dimethylglycine in serum and urine, were increased in the group supplemented with B. lactis compared with the standard formula-fed group. These results support a role of probiotics as effectors of gut microbial activity regulating amino acid utilization and nitrogen cycling. Future risk-benefit analyses are still needed to consolidate the existing knowledge on the long-term consequences of probiotic administration during infancy. IMPORTANCE Probiotics are becoming increasingly popular due to their perceived effects on health, despite a lack of mechanistic information on how they impart these benefits. Infant formula and complementary foods are common targets for supplementation with probiotics. However, different probiotic strains have different properties, and there is a lack of data on long-term health effects on the consumer. Given the increasing interest in supplementation with probiotics and the fact that the gastrointestinal tracts of infants are still immature, we sought to determine whether consumption of infant formula containing the probiotic Bifidobacterium animalis s

There is growing awareness that intestinal microbiota alters the energy harvesting capacity of the host and regulates metabolism. It has been postulated that intestinal microbiota are able to degrade unabsorbed dietary components and transform xenobiotic compounds. The resulting microbial metabolites derived from the gastrointestinal tract can potentially enter the circulation system, which, in turn, affects host metabolism. Yet, the metabolic capacity of intestinal microbiota and its interaction with mammalian metabolism remains largely unexplored. Here, we review a metabolic pathway that integrates the microbial catabolism of methionine with mammalian metabolism of methanethiol (MT), dimethyl sulfide (DMS), and dimethyl sulfoxide (DMSO), which together provide evidence that supports the microbial origin of dimethyl sulfone (DMSO2) in the human metabolome. Understanding the pathway of DMSO2 co-metabolism expends our knowledge of microbial-derived metabolites and motivates future metabolomics-based studies on ascertaining the metabolic consequences of intestinal microbiota on human health, including detoxification processes and sulfur xenobiotic metabolism.

There is growing awareness that intestinal microbiota alters the energy harvesting capacity of the host and regulates metabolism. It has been postulated that intestinal microbiota are able to degrade unabsorbed dietary components and transform xenobiotic compounds. The resulting microbial metabolites derived from the gastrointestinal tract can potentially enter the circulation system, which, in turn, affects host metabolism. Yet, the metabolic capacity of intestinal microbiota and its interaction with mammalian metabolism remains largely unexplored. Here, we review a metabolic pathway that integrates the microbial catabolism of methionine with mammalian metabolism of methanethiol (MT), dimethyl sulfide (DMS), and dimethyl sulfoxide (DMSO), which together provide evidence that supports the microbial origin of dimethyl sulfone (DMSO2) in the human metabolome. Understanding the pathway of DMSO2 co-metabolism expends our knowledge of microbial-derived metabolites and motivates future metabolomics-based studies on ascertaining the metabolic consequences of intestinal microbiota on human health, including detoxification processes and sulfur xenobiotic metabolism.

The human gastrointestinal tract contains a highly complex ecosystem that harbors various microorganisms, which together create a unique environment within each individual. There is growing awareness that dietary habits are one of the essential factors contributing to the microbial diversity and community configuration that ultimately affects human health. From an evolutionary perspective, human dietary history can be viewed as a central factor in the selection of the gut microbial community and stabilization of the mutualistic host-microbial interaction, that together drive host phenotype. Herein, current knowledge concerning the influence of major dietary macrostructure and individual food ingredients is presented. This knowledge will provide perspectives for personalized gut microbiota management and, ultimately, movement toward an era of personalized nutrition and medicine.

Although there is great interest in the specific mechanisms of how gut microbiota modulate the biological processes of the human host, the extent of host-microbe interactions and the bacteria-specific metabolic activities for survival in the co-evolved gastrointestinal environment remain unclear. Here, we demonstrate a comprehensive comparison of the host epithelial response induced by either a pathogenic or commensal strain of Escherichia coli using a multi-omics approach. We show that Caco-2 cells incubated with E. coli display an activation of defense response genes associated with oxidative stress. Indeed, in the bacteria co-culture system, the host cells experience an altered environment compared with the germ-free system that includes reduced pH, depletion of major energy substrates, and accumulation of fermentation by-products. Measurement of intracellular Caco-2 cell metabolites revealed a significantly increased lactate concentration, as well as changes in TCA cycle intermediates. Our results will lead to a deeper understanding of acute microbial-host interactions.

Lithium-ion batteries provide a more cost-effective and non-toxic source of reusable energy compare to other energy sources. Several research studies have lead to production of some more promising cathode components for lithium ion batteries. Recently, a new series of pyrophosphate-based composition Li2FeP2O7 and Li2MnP2O7 has been reported as cathode materials. They have shown a 3D framework structure and the two Lithium-ions in the three-dimensional tunnel structure make it possible that more than one lithium ion be extracted during cycling. Lithium solid state nuclear magnetic resonance (NMR) is an effective technique to study this cathode material, not only for analyzing local structure, but also for investigation of the microscopic processes that take place in the battery. In this work, Li2FeP2O7 and Li2MnP2O7 have been synthesized. The lithium environment of these materials is studied using 1D 6,7Li NMR. Assignment of Li2MnP2O7 spectrum has been made based on Fermi-contact interaction and crystal structure. Both variable temperature experiment and 1D selective inversion NMR are used to establish Li-ion pathways as well as Li hopping rates for Li2MnP2O7. Also, 7Li MAS NMR measurements are used to characterize Li environments in LixFeP2O7 after being electrochemically cycled to different points, and preliminary results regard to changes to ion mobility in LixFeP2O7 at different electrochemical cycled points are presents here, solid-solution (de)lithetiation process is confirmed for this material., Master of Science (MSc)

The human gastrointestinal tract contains a highly complex ecosystem that harbors various microorganisms, which together create a unique environment within each individual. There is growing awareness that dietary habits are one of the essential factors contributing to the microbial diversity and community configuration that ultimately affects human health. From an evolutionary perspective, human dietary history can be viewed as a central factor in the selection of the gut microbial community and stabilization of the mutualistic host-microbial interaction, that together drive host phenotype. Herein, current knowledge concerning the influence of major dietary macrostructure and individual food ingredients is presented. This knowledge will provide perspectives for personalized gut microbiota management and, ultimately, movement toward an era of personalized nutrition and medicine.

Although there is great interest in the specific mechanisms of how gut microbiota modulate the biological processes of the human host, the extent of host-microbe interactions and the bacteria-specific metabolic activities for survival in the co-evolved gastrointestinal environment remain unclear. Here, we demonstrate a comprehensive comparison of the host epithelial response induced by either a pathogenic or commensal strain of Escherichia coli using a multi-omics approach. We show that Caco-2 cells incubated with E. coli display an activation of defense response genes associated with oxidative stress. Indeed, in the bacteria co-culture system, the host cells experience an altered environment compared with the germ-free system that includes reduced pH, depletion of major energy substrates, and accumulation of fermentation by-products. Measurement of intracellular Caco-2 cell metabolites revealed a significantly increased lactate concentration, as well as changes in TCA cycle intermediates. Our results will lead to a deeper understanding of acute microbial-host interactions.