Nutritional and Clinical Glycomics Research

Author: laurenmd (Page 1 of 9)


Alkanaimsh, S., K. Karuppanan, A. Guerrero, A.M. Tu, B. Hashimoto, M.S. Hwang, M.L. Phu, L. Arzola, C.B. Lebrilla, A.M. Dandekar, B.W. Falk, S. Nandi, R.L. Rodriguez, and K.A. McDonald, Transient Expression of Tetrameric Recombinant Human Butyrylcholinesterase in Nicotiana benthamiana. Front Plant Sci, 2016. 7: p. 743.

Arabyan, N., D. Park, S. Foutouhi, A.M. Weis, B.C. Huang, C.C. Williams, P. Desai, J. Shah, R. Jeannotte, N. Kong, C.B. Lebrilla, and B.C. Weimer, Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. Sci Rep, 2016. 6: p. 29525.

Charbonneau, M.R., L.V. Blanton, D.B. DiGiulio, D.A. Relman, C.B. Lebrilla, D.A. Mills, and J.I. Gordon, A microbial perspective of human developmental biology. Nature, 2016. 535(7610): p. 48-55.Awasthi, S., R. Wilken, F. Patel, J.B. German, D.A. Mills, C.B. Lebrilla, K. Kim, S.L. Freeman, J.T. Smilowitz, A.W. Armstrong, and E. Maverakis, Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial. Trials, 2016. 17(1): p. 340.

Charbonneau, M.R., D. O’Donnell, L.V. Blanton, S.M. Totten, J.C. Davis, M.J. Barratt, J. Cheng, J. Guruge, M. Talcott, J.R. Bain, M.J. Muehlbauer, O. Ilkayeva, C. Wu, T. Struckmeyer, D. Barile, C. Mangani, J. Jorgensen, Y.M. Fan, K. Maleta, K.G. Dewey, P. Ashorn, C.B. Newgard, C. Lebrilla, D.A. Mills, and J.I. Gordon, Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition. Cell, 2016. 164(5): p. 859-71.

Davis, J.C., S.M. Totten, J.O. Huang, S. Nagshbandi, N. Kirmiz, D.A. Garrido, Z.T. Lewis, L.D. Wu, J.T. Smilowitz, J.B. German, D.A. Mills, and C.B. Lebrilla, Identification of oligosaccharides in feces of breast-fed infants and their correlation with the gut microbial community. Mol Cell Proteomics, 2016.

Lewis, Z.T., J.C. Davis, J.T. Smilowitz, J.B. German, C.B. Lebrilla, and D.A. Mills, The impact of freeze-drying infant fecal samples on measures of their bacterial community profiles and milk-derived oligosaccharide content. PeerJ, 2016. 4: p. e1612.

Rivera-Chavez, F., L.F. Zhang, F. Faber, C.A. Lopez, M.X. Byndloss, E.E. Olsan, G. Xu, E.M. Velazquez, C.B. Lebrilla, S.E. Winter, and A.J. Baumler, Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella. Cell Host Microbe, 2016. 19(4): p. 443-54.

Ruhaak, L.R., C. Stroble, J. Dai, M. Barnett, A. Taguchi, G.E. Goodman, S. Miyamoto, D. Gandara, Z. Feng, C.B. Lebrilla, and S. Hanash, Serum Glycans as Risk Markers for Non-Small Cell Lung Cancer. Cancer Prev Res (Phila), 2016. 9(4): p. 317-23.

Ruhaak, L.R., K. Kim, C. Stroble, S.L. Taylor, Q. Hong, S. Miyamoto, C.B. Lebrilla, and G. Leiserowitz, Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients. J Proteome Res, 2016. 15(3): p. 1002-10.

Yang, N., E. Goonatilleke, D. Park, T. Song, G. Fan, and C.B. Lebrilla, Quantitation of Site-Specific Glycosylation in Manufactured Recombinant Monoclonal Antibody Drugs. Anal Chem, 2016. 88(14): p. 7091-100.

New Publication in Cell!

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition

Mark R. Charbonneau, David O’Donnell, Laura V. Blanton, Sarah M. Totten, Jasmine C.C. Davis, Michael J. Barratt, Jiye Cheng, Janaki Guruge, Michael Talcott, James R. Bain, Michael J. Muehlbauer, Olga Ilkayeva, Chao Wu, Tedd Struckmeyer, Daniela Barile, Charles Mangani, Josh Jorgensen, Yue-mei Fan, Kenneth Maleta, Kathryn G. Dewey, Per Ashorn, Christopher B. Newgard, Carlito Lebrilla, David A. Mills, Jeffrey I. Gordon

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.

New Blog Post!

After a year of working in the Lebrilla lab on disease biomarkers, Nan was ready to head back to her university in Shanghai.  We had a farewell party at Taste of Thai in Davis.  She’s made much progress in her field of research during her stay, and also was able to make good memories with the group.  Matthew Amicucci was able to sit down and interview Nan about her time here.   Click here and get to know Nan Yang.


New Publication!

The impact of freeze-drying infant fecal samples on measures of their bacterial community profiles and milk-derived oligosaccharide content

1,2, 2,3, 1,2, 1,2,2,3, 1,2,4


Infant fecal samples are commonly studied to investigate the impacts of breastfeeding on the development of the microbiota and subsequent health effects. Comparisons of infants living in different geographic regions and environmental contexts are needed to aid our understanding of evolutionarily-selected milk adaptations. However, the preservation of fecal samples from individuals in remote locales until they can be processed can be a challenge. Freeze-drying (lyophilization) offers a cost-effective way to preserve some biological samples for transport and analysis at a later date. Currently, it is unknown what, if any, biases are introduced into various analyses by the freeze-drying process. Here, we investigated how freeze-drying affected analysis of two relevant and intertwined aspects of infant fecal samples, marker gene amplicon sequencing of the bacterial community and the fecal oligosaccharide profile (undigested human milk oligosaccharides). No differences were discovered between the fecal oligosaccharide profiles of wet and freeze-dried samples. The marker gene sequencing data showed an increase in proportional representation ofBacteriodes and a decrease in detection of bifidobacteria and members of class Bacilli after freeze-drying. This sample treatment bias may possibly be related to the cell morphology of these different taxa (Gram status). However, these effects did not overwhelm the natural variation among individuals, as the community data still strongly grouped by subject and not by freeze-drying status. We also found that compensating for sample concentration during freeze-drying, while not necessary, was also not detrimental. Freeze-drying may therefore be an acceptable method of sample preservation and mass reduction for some studies of microbial ecology and milk glycan analysis.

2015 Publications

Dallas, D.C., A. Guerrero, E.A. Parker, R.C. Robinson, J. Gan, J.B. German, D. Barile, and C.B. Lebrilla, Current peptidomics- Applications, purification, identification, quantification, and functional analysis. Proteomics, 2015. 15(5-6): p. 1026-38.

Dallas, D.C., C.J. Smink, R.C. Robinson, T. Tian, A. Guerrero, E.A. Parker, J.T. Smilowitz, K.A. Hettinga, M.A. Underwood, C.B. Lebrilla, J.B. German, and D. Barile, Endogenous Human Milk Peptide Release Is Greater after Preterm Birth than Term Birth. J Nutr, 2015. 145(3): p. 425-33.

De Leoz, M.L., K.M. Kalanetra, N.A. Bokulich, J.S. Strum, M.A. Underwood, J.B. German, D.A. Mills, and C.B. Lebrilla, Human Milk Glycomics and Gut Microbial Genomics in Infant Feces Show a Correlation between Human Milk Oligosaccharides and Gut Microbiota- A Proof-of-Concept Study. J Proteome Res, 2015. 14(1): p. 491-502.

Guerrero, A., D.C. Dallas, S. Contreras, A. Bhandari, A. Canovas, A. Islas-Trejo, J.F. Medrano, E.A. Parker, M. Wang, K. Hettinga, S. Chee, J.B. German, D. Barile, and C.B. Lebrilla, Peptidomic analysis of healthy and subclinically mastitic bovine milk. Int Dairy J, 2015. 46: p. 46-52.

Guerrero, A., L. Lerno, D. Barile, and C.B. Lebrilla, Top-Down Analysis of Highly Post-Translationally Modified Peptides by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. J Am Soc Mass Spectrom, 2015. 26(3): p. 453-9.

Hong, Q., L.R. Ruhaak, C. Stroble, E. Parker, J. Huang, E. Maverakis, and C.B. Lebrilla, A Method for Comprehensive Glycosite-Mapping and Direct Quantitation of Serum Glycoproteins. J Proteome Res, 2015.

Huang, J., A. Guerrero, E. Parker, J.S. Strum, J.T. Smilowitz, J.B. German, and C.B. Lebrilla, Site-specific Glycosylation of Secretory Immunoglobulin A from Human Colostrum.  J Proteome Res, 2015. 14(3): p. 1335-49.

Krishnan, S., J. Huang, H. Lee, A. Guerrero, L. Berglund, A. Erdembileg, C.B. Lebrilla, and A.M. Zivkovic, Combined HDL proteomic and glycomic profiles in patients at risk for coronary artery disease.. J Proteome Res, 2015.

Lewis, Z.T., S.M. Totten, J.T. Smilowitz, M. Popovic, E. Parker, D.G. Lemay, M.L. Van Tassell, M.J. Miller, Y.S. Jin, J.B. German, C.B. Lebrilla, and D.A. Mills, Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants.. Microbiome, 2015. 3: p. 13.

Maverakis, E., K. Kim, M. Shimoda, M.E. Gershwin, F. Patel, R. Wilken, S. Raychaudhuri, L.R. Ruhaak, and C.B. Lebrilla, Glycans in the immune system and The Altered Glycan Theory of Autoimmunity- A critical review. J Autoimmun, 2015. 57: p. 1-13.
Mechref, Y. and C. Lebrilla, 30th ASMS Asilomar Conference on Advances in Glycomics and Glycoproteomics: Methods and Applications. J Am Soc Mass Spectrom, 2015. 26(7): p. 1047-50.

Park, D., K.A. Brune, A. Mitra, A.I. Marusina, E. Maverakis, and C.B. Lebrilla, Characteristic changes in cell surface glycosylation accompany intestinal epithelial cell differentiation: high mannose structures dominate the cell surface glycome of undifferentiated enterocytes. Mol Cell Proteomics, 2015.

Ruhaak, L.R., D.A. Barkauskas, J. Torres, C.L. Cooke, L.D. Wu, C. Stroble, S. Ozcan, C.C. Williams, M. Camorlinga, D.M. Rocke, C.B. Lebrilla, and J.V. Solnick,The serum immunoglobulin G glycosylation signature of gastric cancer EuPA Open Proteom, 2015. 6: p. 1-9.

Ruhaak, L.R. and C.B. Lebrilla, Applications of Multiple Reaction Monitoring to Clinical Glycomics, 2015. 78(5-6): p. 335-342.

Ruhaak, L.R., S.L. Taylor, C. Stroble, U.T. Nguyen, E.A. Parker, T. Song, C.B. Lebrilla, W.N. Rom, H. Pass, K. Kim, K. Kelly, and S. Miyamoto, Differential N-glycosylation patterns in lung adenocarcinoma tissue. J Proteome Res, 2015.

Song, T., D.L. Aldredge, and C.B. Lebrilla, A method for in-depth structural annotation of human serum glycans yields the biological variations. Anal Chem, 2015.

Underwood, M.A., J.B. German, C.B. Lebrilla, and D.A. Mills, Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res, 2015. 77(1-2): p. 229-35.

Wang, M., M. Li, S. Wu, C.B. Lebrilla, R.S. Chapkin, I. Ivanov, and S.M. Donovan, Fecal microbiota composition of breast-fed infants is correlated with human milk oligosaccharides consumed.. J Pediatr Gastroenterol Nutr, 2015. 60(6): p. 825-33.

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New Publications!

Hong, Q., et al. (2015). “A Method for Comprehensive Glycosite-Mapping and Direct Quantitation of Serum Glycoproteins.” J Proteome Res.
A comprehensive glycan map was constructed for the top eight abundant glycoproteins in plasma using both specific and non-specific enzyme digestions followed by nano LC-Chip/QTOF mass spectrometry (MS) analysis. Glycopeptides were identified using an in-house software tool, GPFinder. A sensitive and reproducible multiple reaction monitoring (MRM) technique on a triple quadrupole MS was developed and applied to quantify immunoglobulins G, A, M, and their site-specific glycans simultaneously and directly from human serum/plasma without protein enrichments. A total of 64 glycopeptides and 15 peptides were monitored for IgG, IgA, and IgM in a 20-min UPLC gradient. The absolute protein contents were quantified using peptide calibration curves. The glycopeptide ion abundances were normalized to the respective protein abundances to separate protein glycosylation from protein expression. This technique yields higher method reproducibility and less sample loss when compared with the quantitation method that involves protein enrichments. The absolute protein quantitation has a wide linear range (3-4 orders of magnitude) and low limit of quantitation (femtomole level). This rapid and robust quantitation technique, which provides quantitative information for both proteins and glycosylation, will further facilitate disease biomarker discoveries.

Krishnan, S., et al. (2015). “Combined HDL proteomic and glycomic profiles in patients at risk for coronary artery disease..” J Proteome Res.
OBJECTIVES: To test whether recently developed methods for comprehensive profiling of the HDL glycome combined with the HDL proteome can distinguish individuals with coronary artery disease (CAD) from those without. METHODS: Twenty subjects, at risk for CAD, who underwent diagnostic coronary arteriography were analyzed. Ten subjects had CAD, and ten did not. HDL were extracted from fasting plasma samples by ultracentrifugation, followed by shotgun proteomic, glycomic and ganglioside analyses using LC-MS. CAD vs. non-CAD subjects’ data were compared using univariate and multivariate statistics. RESULTS: Principal components analysis showed a clear separation of CAD and non-CAD subjects, confirming that combined HDL proteomic and glycomic profiles distinguished at-risk subjects with atherosclerosis from those without. CAD patients had lower HDL apolipoprotein content (specifically Apo AI, AII and E, p <0.05), and lower serum amyloid A2 (SAA2, p = 0.020) and SAA4 (p = 0.007) but higher sialylated glycans (p<0.05). CONCLUSION: Combined proteomic and glycomic profiling of isolated HDL was tested as a novel analytical approach for developing biomarkers of disease. In this pilot study we found that HDL proteome and glycome distinguished between individuals who had CAD from those who did not within a group of individuals equally at risk for heart disease.

Park, D., et al. (2015). “Characteristic Changes in Cell Surface Glycosylation Accompany Intestinal Epithelial Cell (IEC) Differentiation: High Mannose Structures Dominate the Cell Surface Glycome of Undifferentiated Enterocytes.” Mol Cell Proteomics.
Changes in cell surface glycosylation occur during the development and differentiation of cells and have been widely correlated with the progression of several diseases. Due to their structural diversity and sensitivity to intra- and extracellular conditions, glycans are an indispensable tool for analyzing cellular transformations. Glycans present on the surface of intestinal epithelial cells (IEC) mediate interactions with billions of native microorganisms, which continuously populate the mammalian gut. A distinct feature of IECs is that they differentiate as they migrate upwards from the crypt base to the villus tip. In this study, nano-LC/ESI QTOF MS profiling was used to characterize the changes in glycosylation that correspond to Caco-2 cell differentiation. As Caco-2 cells differentiate to form a brush border membrane, a decrease in high mannose type glycans and a concurrent increase in fucosylated and sialylated complex/hybrid type glycans were observed. At day 21, when cells appear to be completely differentiated, remodeling of the cell surface glycome ceases. Differential expression of glycans during IEC maturation appears to play a key functional role in regulating the membrane-associated hydrolases and contributes to the mucosal surface innate defense mechanisms. Developing methodologies to rapidly identify changes in IEC surface glycans may lead to a rapid screening approach for a variety of disease states affecting the GI tract.


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