Source: UNIVERSITY OF CALIFORNIA, DAVIS submitted to
STUDIES ON THE MICROORGANISMS ASSOCIATED WITH FOODS AND BEVERAGES
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
HATCH
Reporting Frequency
Annual
Accession No.
1004163
Grant No.
(N/A)
Project No.
CA-D-FST-6568-H
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Nov 6, 2014
Project End Date
Sep 30, 2019
Grant Year
(N/A)
Project Director
Mills, D.
Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Performing Department
Food Science and Technology
Non Technical Summary
My research focuses in two primary areas. We are examining the microbiota associated with food production facilities and food production processes in order to link microbiota constitution, the cognate microbiome functional attributes and their biogeographical relationships to food quality and safety. In a second area we are focused on examination of food molecules that perform bioactive functions in situ, particularly modulating the intestinal microbiome and its function and relationship to the host.
Animal Health Component
0%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
5023450110030%
5034010110010%
7013450110025%
7043450110025%
7124010110010%
Knowledge Area
712 - Protect Food from Contamination by Pathogenic Microorganisms, Parasites, and Naturally Occurring Toxins; 503 - Quality Maintenance in Storing and Marketing Food Products; 704 - Nutrition and Hunger in the Population; 502 - New and Improved Food Products; 701 - Nutrient Composition of Food;

Subject Of Investigation
4010 - Bacteria; 3450 - Milk;

Field Of Science
1100 - Bacteriology;
Goals / Objectives
The goals of this project are to:1. Characterize food and beverage-related microbes and microbial biogeography using molecular methods.2. Characterize the molecular biology and physiology of probiotic lactic acid bacteria and bifidobacteria. 3. Characterize bioactive ingredients in milk and novel prebiotics for their impact on gut health.
Project Methods
We will employ various techniques to perform our research including:1. Next generation marker gene sequencing to map microbial ecologies of food production systems or gut microbiomes2. Mass spectrometry based glycomics to analyze breakdown of prebiotic molecules to define how probiotics3. Mass spectrometry and NMR based metabolomics to examine metabolites produced by food- or gut-related microbes4. Next generation sequencing to enable metagenomic, metatranscriptomic, transcriptomic and genomic characterization of microbial consortia or individual microbes or eukaryotic cell responses to these microbes.5. Novel molecular genetic techniques to examine gene function in lactic acid bacteria and bifidobacteria6. Employ mouse and pig animal models of gut health or dysbiosis.

Progress 11/06/14 to 09/30/19

Outputs
Target Audience:The main target audience for our microbial ecology work is the food, wine and biofuel industries. Our work on food glycans/bifidobacteria/intestinal health is of great interest to the food industry and the pharmaceutical industry Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?In past five years I advised 8 scientific staff, 7 postdoctoral fellows, 6 PhD students, 2 MS students, and >30 undergraduate students. During this period nearly all of my students presented their research at local and international meetings and others have obtained topic-specific training. How have the results been disseminated to communities of interest?In the past year I have presented my research at numerous stakeholders, commodity oriented meetings, national and international meetings including: "A naturally evolved system to enrich a beneficial gut microbiome: the wonders of human milk". 7th Annual Southern California Microbiome Symposium: Connections to the Environment and Health, UC Irvine, Irvine CA. Sept. 20, 2019. "The role of milk oligosaccharides in the development, persistence and function of the breast fed infant gut microbiome". Gordon Research Conference--Applied Environmental Microbiology, South Hadley, MA. July 14-19, 2019. "The microbiota, gut, and brain in neurodevelopment and autism: Integrating Chemistry, Ecology and Physiology". Research Seminar Series--MIND Institute, UC Davis Medical School. Sacramento, CA. June 14, 2019. "Lessons learned from a naturally evolved system to enrich a functional microbiome: The wonders of mammalian milk" Elements--UC Davis Comprehensive Cancer Center Initiative Symposium, Sacramento, CA. March 7, 2019. "Mammals, milk and microbes--The role of milk in the establishment and function of the gut microbiome". Medical College of Wisconsin Center for Microbiome Research. Milwaukee, WI. February 12, 2019. "Lessons learned from a naturally evolved system to enrich a functional microbiome: The wonders of mammalian milk" Plant and Animal Genome XXVII Conference, San Diego, CA. January 13, 2019. "Milk oligosaccharides and their role in neonatal health: Lessons for tailored synbiotics". Food Innovation and Engineering Conference--AIChE. Napa, CA December 3, 2018. "Mammals, milk and microbes--The role of milk in the establishment and function of the gut microbiome". 2nd Symposium on Probiotics, Gut Microbiome & Health (PGuMH2018), Wuxi, China. Oct 26, 2018. "Diet drives assembly of livestock resistome during early life". AgResearch NZ, Palmerston North, New Zealand, August 31, 2018. "Milk oligosaccharides and their role in neonatal health: Lessons for tailored synbiotics". New Zealand Dairy Industry Workshop, Palmerston North, New Zealand, August 29, 2018. "Mammals, Milk and Microbes: The role of milk in the establishment and function of the neonate gut microbiome". Seoul National University, Seoul, Korea, July 3, 2018. "Mammals, Milk and Microbes: The role of Milk in the Establishment and Function of the Neonate gut Microbiome". Korea Yakult Central Research Institute, Seoul, Korea, July 2, 2018. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? My research centers on the ecology, genetics and genomics of the microbes present in food or involved in intestinal health. The period under review (Nov 2014-Sept 2019) has been productive resulting in ~80 publications and 5 book chapters (some discussed below). This work has focused on three main topics: the microbiology of gut health, the molecular ecology of food microbes and various methodological studies. Gut Health. I have continued to research the fundamental basis for how milk directs the development of the newborn intestine and its microbiome. Working with Profs Lebrilla (CHE), Barile (FST), Dewey (NUT) and Prof Jeff Gordon (Washington Univ), we published a seminal paper in Cell defining a molecular basis for how bovine milk oligosaccharides (BMOs) promote lean body mass in mouse and pig models of malnutrition [PMC4793393]. This theme was advanced further in two publications with Profs Raybould (VetMed) and Barile which defined how BMOs improve barrier function and lower inflammation in mouse models of dysbiosis [PMC5451559,PMC5481169]. Finally I participated in a study led by Prof Barile and Dr. Smilowitz (FST) demonstrating the tolerability and safety of BMO in a feeding trial [PMC5465862]. We also carried out an important study with Prof German and Lebrilla, showing that the genotype of the mother, expressed through the milk glycome, influences the eventual gut microbiota of the breast fed infant [PMC4412032]. This work was extended with Georgian and Armenian collaborators characterizing the nursing infant gut microbiota in two cohorts of these neighboring countries [PMC5288704]. With Profs Underwood (UCDMC) and Lebrilla we examined how milk oligosaccharides influence the premature infant gut microbiota [PMC4689671] and how supplemented Bifidobacterium breve impacts that community function [PMC6349036]. With Prof Zivkovic (NUT) and Lebrilla we characterized the intersection of milk oligosaccharides and gut microbes on the health status of Gambian infants [PMC5227965], demonstrating that the concentration of lacto-N-fucopentose I in the mothers' milk was associated with decreased infant morbidity. With Profs Lebrilla and German we examined the specific fecal glycoprofiles linked it to specific glycosidases within the infant gut microbiome [PMC5013312] providing mechanistic insight into oligosaccharide degradation in situ as well as diagnostic opportunities for proper digestion. With Prof Underwood we examined the benefit of probiotic supplementation in infants with gastroschisis [PMC4854817] and characterized the oral microbiome associated with buccal administration of human colostrum [PMID: 26658119]. With Prof Calvert (ANS) we characterized the nursing to weaning metagenome of piglets defining key microbial degradation patterns suggesting cross feeding of milk oligosaccharides between bacteroidales and enterobactericae [PMC4499176]. Subsequent work with Prof Barile further characterized the pig milk oligosaccharides and their link to this piglet gut microbiome [PMC5557353] and to show that Bifidobacterium longum subsp. infantis (B. infantis) can digest and grow on milk gangliosides [PMC4048636]. We also showed that bifidobacteria grow amazingly well on the released glycans but poorly on the milk glycoproteins [PMC4959171], providing fundamental mechanistic insight on infant milk glycoprotein digestion while simultaneously demonstrating the prebiotic activity of the released oligosaccharides and a means to obtain them. I also worked with Prof Chen (CHE) to characterize the specific growth behavior of bifidobacteria on enzymatically synthesized lacto-N-fucopentose I, a prominent human milk oligosaccharide [PMC4775349]. I was involved in a range of other studies examining bifidobacterial function in vivo. With Prof. Slava Dvorak (U. Arizona) and Prof. Mark Underwood (PED) we demonstrated how provision of B. infantis modulates the gut microbiota and is protective against necrotizing enterocolitis in a mouse pup model [PMC4167942]. Working with Prof. Lebrilla we demonstrated that milk glycans disappear from term infant feces concurrent with increases in bifidobacterial populations [PMC4286166 ], providing the first in vivo evidence of milk glycan consumption by infant gut microbiomes, illustrating how glycans are useful diagnostic markers for health in the nursing infant. Working with Prof. Underwood we also showed how application of prebiotics alone in premature infants does not increase bifidobacterial levels and actually increased levels of Proteobacteria, a potentially harmful clade [PMID: 24135979]. Lastly I worked with Dr. Charles Stephensen (USDA) on a cohort of breast fed infants from Bangladesh and showed positive correlation between bifidobacterial levels, and B. infantis in particular, with a robust response for various vaccines received in the first year of life [PMC4187229]. Working with Prof. Andy Waterhouse we characterized the changing micorbiota of piglets fed grape seed proanthocyanidins [PMC4744461]. Working with Dr. Elizabeth Maga we examined the microbiota of freshly expressed goat milk and compared it to the "milk microbiome" transgenic goat that express human lysozyme in their milk [PMID: 25475275]. We provided bioinformatics assistance on a fascinating glycomic study of tissue samples taken from four mummies which were naturally preserved [PMC4894394]. In addition, I collaborated with Prof Noratto (Texas A&M) on the impact of fiber supplementation on a mouse model of obesity [PMID: 28815303, PMC4768707]. Finally I have worked with colleagues to summarize our results in this area with 9 reviews/commentaries. Food/Beverage Microbiology. My lab continues to pioneer use of next generation sequencing (NGS) to interrogate the complete microbial ecology of food/beverage production environments and products. During this period we worked with Prof Bamforth detailing the microbial population changes occurring in a lambic-style brewery [PMC4352708]. Working with Profs Heyman (VEN) and Ebeler (VEN), we detailed associations between grape must microbiota, fermentation performance, and finished wine properties [PMC4959672]. This multidisciplinary effort advances the concept of a nonrandom "microbial terroir" contributing to final flavor attributes of wine. With collaborators in Armenia and Georgia we used NGS to examine a range of additional fermentations including: regional influences in fermented Matsoni (a fermented milk; [PMID: 25998810]); microbiota shifts that occur during cheese spoilage with Prof Jim Steele (U Wisconsin)[PMID: 25846916], and combined metagenomics and proteomics characterization of fermented kefir [PMC4664887]. We also used a range of molecular ecology techniques to profile the complete production of sake in a facility in Texas that carries out traditional production style [PMC4136118]. Methods development. My lab is exploring methods to obtain and validate novel streams of milk oligosaccharides. Working with Profs Barile, Block and Bell, we characterized the parameters for optimal release of bovine milk oligosaccharides from milk glycoproteins [PMC4623841, PMC4623945, PMC4733529] using a endo-β-N-acetylglucosaminidase previously discovered in my lab. I have worked with Dr. Lemay (USDA) and Prof Korf (MCB) on the development of novel bioinformatic methods to characterize metatranscriptomes [PMC5963165, PMC5041328]. I also worked with Prof Kim (Chungnam National University) on a comparative proteomics method initially developed when he was in my laboratory [PMC4704264]. With Profs Lebrilla and German, we demonstrated that freeze drying of feces minimally influences microbiota and oligosaccharide measurements [PMC4727960 ] thereby assisting in field studies. Finally, we developed a method to differentiate B. longum subspecies and showed how many current commercial probiotics do not contain the species named on their label [PMC4916961].

Publications

  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Lueschow, S. R., J. Stumphy, H. Gong, S. L. Kern, T. G Elgin, M. A. Underwood, K. M. Kalanetra, D. A. Mills, M. H. Wong, D. K. Meyerholz, M. Good, and S. J. McElroy. 2018. Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis. PLOS One 13:e0204967
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Sanctuary, M. R., J. N. Kain, S. Chen, K. Kananetra, D. G. Lemay, D. R. Rose, H. T. Yang, D. J. Tancredi, J. B. German, C. M. Slupsky, P. Ashwood, D. A. Mills, J. T. Smilowitz, K. Angkustisiri. 2019. Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms. PLOS One 14:e0210064.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Huda, N. M., S. M. Ahmad, K. M. Kalanetra, D. H. Taft, M. J. Alam,A. Khanam, R. Raqib, M. A. Underwood, D. A. Mills, C. B. Stephensen. 2019. Neonatal vitamin A supplementation and vitamin A status are associated with gut microbiome composition in Bangladeshi infants in early infancy and at two years of age. J. Nutrition 149:1075-1088.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Taft, D. H., L. K. Salinero, K. Vongbhavit, K. M. Kalanetra, C. Masarweh, A. Yu, M. A. Underwood, D. A. Mills. 2019. Bacterial colonization and antimicrobial resistance genes in neonatal enteral feeding tubes. FEMS Microbial Ecology 95:fiz039.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Cowardin, C. A., P. P. Ahern, V. L. Kung, M. C. Hibberd, J. Cheng, J. L. Guruge, V. Sundaresan, R. D. Head, D. Barile, D. A. Mills, M. J. Barratt, S. Huqg, T. Ahmed, and J. I. Gordon. Mechanisms by which sialylated milk oligosaccharides impact bone biology in a gnotobiotic mouse model of infant undernutrition. Proceedings of the National Academy of Science 116:11988-11996.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Liu, J., D. H. Taft, M. X. Maldonado-Gomez, D. Johnson, M. L. Treiber, D. G. Lemay, E. J. DePeters and D. A. Mills. 2019. The fecal resistome of dairy cattle is associated with diet during nursing. Nature Communications 10:4406.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Elgin T.G., E. M. Fricke, H. Gong, J. Reese, D. A. Mills, K. M. Kalantera, M. A. Underwood and S. J. McElroy. 2019. Fetal exposure to maternal inflammation interrupts murine intestinal development and increases susceptibility to neonatal intestinal injury. Disease Models & Mechanisms. 12:dmm040808.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Liu, S., C. Skory, X. Liang, D. A. Mills, and N. Qureshi. 2019. Increased ethanol tolerance associated with the pntAB locus of Oenococcus oeni and Lactobacillus buchneri. Journal of Industrial Microbiology and Biotechnology 46:1547-1556.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Taft, D. H., S. Akre, N. Madrid, A. Knoesen, D. A. Mills and Z. T. Lewis. 2019. Resident microbes of lactation rooms and daycares. PeerJ 7:e8168.


Progress 10/01/17 to 09/30/18

Outputs
Target Audience:The main target audience for our microbial ecology work is the food, wine and biofuel industries. Our work on food glycans/bifidobacteria/intestinal health is of great interest to the food industry and the pharmaceutical industry Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?In the last year I advised 5 scientific staff, 4 postdoctoral fellows, 5 PhD students, 2 MS students, and 10 undergraduate students. During this period some of my students presented their research at local and international meetings and others have obtained topic specific training. How have the results been disseminated to communities of interest?In the past year I have presented my research at numerous commodity oriented meetings, national and international meetings including: "Mammals, Milk and Microbes: The role of Milk in the Establishment and Function of the Neonate gut Microbiome". Korean Society for Food Science & Technology Annual Meeting, Busan, Korea, June 28, 2018. "Mammals, Milk and Microbes: The role of Milk in the Establishment and Function of the Neonate gut Microbiome". FASEB Meeting on Nutritional Immunology and the Microbiota: Rules of Engagement in Health and Disease, Leeburg, VA, June 26, 2018. "Mammals, Milk and Microbes: The role of Milk in the Establishment and Function of the Neonate gut Microbiome". University of Florida Medical School, Gainesville, FL, March 20, 2018. "Mammals, Milk and Microbes: The role of Milk in the Establishment and Function of the Neonate gut Microbiome". Nutrition and Growth Conference, Paris, France, March 1, 2018. "Childhood Undernutrition and the Gut Microbiota in the First 1000 Days", 2nd Annual Abbott Nutrition Growth Summit, Paris, France, Feb 28, 2018. "Mammals, Milk and Microbes: The role of Milk in the Establishment and Function of the Neonate gut Microbiome". Baylor College of Medicine, Houston, TX, Feb 8, 2018. "Mammals, Milk and Microbes--The role of milk in the establishment and function of the gut microbiome" 2018 Academia Sinica - UC Davis Bilateral Symposium, Davis, CA, Jan 22-23, 2018. "Mammals, Milk and Microbes--The role of milk in the establishment and function of the gut microbiome" 4th International Conference on Microbial Diversity, Bari, Italy. Oct 24-26, 2017. "Impact of breast milk on the development of the infant gut microbiome: Implications for health and development in the first 1000 days". 10th World Congress on the Developmental Origins of Health and Disease, Rotterdam, The Netherlands. Oct. 17, 2017. "Contributions of the built environment to microbial ecology of dairies and wineries", Microbiology of the Built Environment (MoBE) 2017 Symposium, The National Academy of Science, Washington DC, Oct 11, 2017. "Mammals, Milk and Microbes--The role of milk in the establishment and function of the gut microbiome" Distinctive Voices--National Academies of Sciences, Engineering and Medicine; Irvine, CA, Sept. 20, 2017. What do you plan to do during the next reporting period to accomplish the goals?I will continue to do research and extension in the area of food and gut microbiology. I will publish research, present seminars, train students and teach classes and short courses. I will also interface directly with stakeholders.

Impacts
What was accomplished under these goals? The goals of this project are to: 1. Characterize the molecular biology and physiology of lactic acid bacteria and bifidobacteria. 2. Characterize bioactive ingredients and novel prebiotics for their impact on gut health. I have continued to research the fundamental basis for how milk directs the development of the newborn intestine and its microbiome. During the period under review my work focused analysis of synbiotic applications of bifidobacteria and milk oligosaccharides or analysis of infant populations naturally high in bifidobacteria during nursing. The latter work defined how antimicrobial resistance genes are lower in the gut metagenomes of infants dominated by milk-oligosaccharide consuming bifidobacteria. I also worked to define how breast fed infants supplemented with a milk oligosaccharide-consuming bifidobacteria led to persistent and dominant colonization of those infants with dramatic changes in their fecal biochemistries. I have an NIH grant with Profs Wan (UCDMC) and Slupsky (FST) focused on methods to reduce liver cancer via suppression of intestinal dysbiosis and associated inflammation using supplemented milk oligosaccharides and bifidobacteria. In the period under review we published a paper showing that synbiotic application of milk oligosaccharides and Bifidobacterium infantis reverses cancer-prone non-alcoholic steatohepatitis in a mouse model. Finally, we also published two reviews on the relationship between bifidobacteria and milk oligosaccharides. Working with Patricia Oteiza (NUT) we characterized how epicatichin modulated the gut microbiota and protected barrier function in a mouse model of high fat diet induced inflammation. We also published a review on the interaction of flavonoids and the GI tract. I have an ongoing collaboration with Prof Noratto (Texas A&M) focused on the impact of fiber supplementation on the gut microbiota in a mouse model of obesity. During this period we published a paper on the effects of barley supplementation on an obese mouse model. My lab has also continued to work on methods development for microbiota analysis. During the period under review we collaborated with Danelle Lemay (USDA) to publish and upgrade on a metatranscriptome analysis pipeline. Finally, as part of collaboration with Prof Scott McElroy (U Iowa) and Mark Underwood (UCDMC) we examined aspects of lipopolysaccharide-induced maternal inflammation influences gut microbiome changes and fetal injury--resulting in a publication.

Publications

  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Frese, S., A. Hutton, L. Contreras, C. Shaw, M. Palumbo, G. Casaburi, G. Xu, J. Davis, C. Lebrilla, B. Henrick, S. Freeman, D. Barile, J. B. German, D. A. Mills, J. Smilowitz, M. Underwood. Persistence of supplemented Bifidobacterium longum subsp. infantis EVC001 in breastfed infants. mSphere 2: e00501-17.
  • Type: Book Chapters Status: Published Year Published: 2017 Citation: Shani, G. I., Z. T. Lewis, A. M. Robinson and D. A. Mills. 2017. In, The Bifidobacteria and Related Organisms, Biavati, B. W. H. Holzapfel, P. Mattarelli and B. J. B. Wood Eds. Interactions between bifidobacteria, milk oligosaccharides and neonate hosts. p165-175. Elsevier, New York, New York.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Garcia-Mazcorro, J. F., D. A. Mills, K. Murphy, G. Noratto. 2018. Effect of barley supplementation on the fecal microbiota, caecal biochemistry and key biomarkers of obesity and inflammation in obese db/db mice. European Journal of Nutrition. 57:2513-2528.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Kirmiz, N., R. C. Robinson, I. M. Shah, D. Barile and D. A. Mills. 2018. Milk glycans and their interaction with the infant gut microbiota. Annual Review in Food Science & Technology 9:429-450.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Cremonini, E., Z. Wang, A. Bettaie, A. M. Adamo, E. Daveri, D. A. Mills, K. Kalanetra, F. G. Hajb, P. I. Oteiza. 2018. Epicatechin protecs the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance. Redox Biology 14:588-599.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Fricke, E. M., T. G. Elgin, H. Gong, J. Reese, K. Gibson-Corley, R. Weiss, K. Zimmerman, N. C. Bowdler, K. M. Kalantara, D. A. Mills, M. A. Underwood, S. J. McElroy. 2018. Lipopolysaccharide-induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood. Placenta 79:e12816.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Oteiza, P. I., C.G. Fragaa, D.A. Mills, D.H. Taft. 2018. Flavonoids and the gastrointestinal tract: Local and systemic effects. Molecular Aspects of Medicine 61:41-49.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Kumar P. J., C. Wu, D. A. Mills, N. Nagar, D. Barile, L. Sheng, Y.J. Wan. 2018. Synbiotics Bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone non-alcoholic steatohepatitis using Western diet-fed FXR knockout mouse models. J. Nutritional Biochemistry 57:246-254.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Westreich, S. T., M. L. Treiber, D. A. Mills, I. Korf, D. G. Lemay. 2018. SAMSA2: A standalone metatranscriptome analysis pipeline. BMC Bioinformatics 19:175.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Bever, C. S., A. A. Rand, M. Nording, D. Taft, K. M. Kalanetra, D. A. Mills, M. A Breck, J. T. Smilowitz, J B. German, B. D. Hammock. Effects of triclosan in breast milk on the infant fecal microbiome. Chemosphere 203:467-473.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Taft, D. H., J. Liu, M. X. Maldonado-Gomez, S. Akre, M. N. Huda, S.M. Ahmad, C. B. Stephensen and D. A. Mills. 2018. Bifidobacterial dominance of the gut in early life and acquisition of antimicrobial resistance. mSphere e00441-18.


Progress 10/01/16 to 09/30/17

Outputs
Target Audience:The main target audience for our microbial ecology work is the food, wine and biofuel industries. Our work on milk glycans/bifidobacteria/intestinal health is of great interest to the infant formula industry, the dairy industry and the pharmaceutical industry Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?In the last year I advised 4 scientific staff, 4 postdoctoral fellows, 5 PhD students, 2 MS students, and 10 undergraduate students. During this period some of my students presented their research at local and international meetings. How have the results been disseminated to communities of interest?In the past year I have presented my research at numerous commodity oriented meetings, national and international meetings. "New insight on how milk "farms" the neonate gut microbiota", International Symposium on Milk Genomics and Human Health, Sept 27, 2016, Davis, CA. "Establishment of a milk-oriented microbiota (MOM) in infants: What a MOM can tell us about effective probiotics and prebiotics" University of Minnesota Healthy Foods, Heathy Lives Institute Symposium on Food, Microbes and Health, Minneapolis, MN, Oct. 27, 2016. "Microbial colonization patterns in mammalian neonates--how milk in "farms" the infant gut microbiota" International Human Microbiome Consortium (IHMC) Congress, Houston, TX, Nov. 10, 2016. "New insights on benefit of breast-feeding: Endogenous pre- and probiotics in breastmilk", Advances and Controversies in Clinical Nutrition, Orlando, FL Dec 8, 2016. "A molecular basis for a milk glycome-driven formation of the infant gut microbiota", International Union of Biochemistry and Molecular Biology - Frontiers in Glycoscience: Host-pathogen interactions, Taipai, Taiwan, Dec 12, 2016. "Restoring ecosystem function in the infant microbiome". Precision Medicine Conference, San Jose, CA. Jan 23, 2017. "The microbial ecology of coffee production." Sensory Summit: A Roasters Guild Event, Davis, CA. Jan 27, 2017. "Microbial colonization patterns in mammalian neonates--how milk in "farms" the infant gut microbiota". Northern California Branch of the American Society for Microbiology. Pleasanton, CA. March 3, 2017. "Milk oligosaccharide cross-feeding as a mechanism for pathogen expansion in NEC". Necrotizing Enterocolitis Symposium: A Transdisciplinary Approach to Improved Outcomes. Sacramento, CA. April 5 - 7, 2017."Lessons learned from a milk-driven enrichment of the infant gut microbiota: Implications for novel prebiotics and probiotics". Natural Products Expo West. Anaheim, CA. March 9, 2017. "Milk oligosaccharide cross-feeding as a mechanism for pathogen expansion in NEC". Necrotizing Enterocolitis Symposium: A Transdisciplinary Approach to Improved Outcomes. Sacramento, CA. April 5 - 7, 2017. "Mopping up spilled milk: Restoring ecosystem function in the nursing infant gut microbiome." Congress on Gastrointestinal Function, Chicago, IL. April 10, 2017. "Mammals, Milk and Microbes--The role of milk in the establishment and function of the gut microbiome" Etchells Memorial Lecturer, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, April 27, 2017. "The microbiome of foods and their production: A new look at the microbes that make, or spoil, our foods." California Academy of Nutrition and Dietetics Meeting: Shaping the Future of a Healthier California, Sacramento, CA. April 29, 2017. "Contributions of the built environment to microbial ecology of cheese", American Dairy Science Association Annual Meeting, Pittsburg, PA. June 28, 2017."Mammals, Milk and Microbes--The role of milk in the establishment and function of the gut microbiome" Distinctive Voices--National Academies of Sciences, Engineering and Medicine; Irvine, CA, Sept. 20, 2017. What do you plan to do during the next reporting period to accomplish the goals?I will continue to do research and extension in the area of food microbiology. I will publish research, present seminars, train students and teach classes and short courses. I will also interface directly with stakeholders.

Impacts
What was accomplished under these goals? The goals of this project are to: 1. Characterize the molecular biology and physiology of probiotic lactic acid bacteria and bifidobacteria. 2. Characterize bioactive ingredients in milk and novel prebiotics for their impact on gut health. Milk influence on gut health. I have continued to research the fundamental basis for how milk directs the development of the newborn intestine and its microbiome. During the period under review my work focused in three general areas: milk oligosaccharides, milk influences on infant gut microbiota and milk/microbe interactions with the infant host. Working with Profs Raybould (VetMed) and Barile which defined how bovine milk oligosaccharides improve barrier function and lower inflammation in mouse models of dysbiosis. Finally I participated in a study led by Prof Barile and Dr. Smilowitz demonstrating the tolerability and safety of BMO in a feeding trial. Working with Georgian and Armenian collaborators we characterized the nursing infant gut microbiota in two cohorts of these neighboring countries. With Profs Underwood (UCDMC) we examined how supplemented Bifidobacterium breve impacts that community function. With Prof Zivkovic (NUT) and Prof Lebrilla (CHEM) we characterized the intersection of milk oligosaccharides and gut microbes on the health status of Gambian infants, demonstrating that the concentration of lacto-N-fucopentose I in the mothers' milk was associated with decreased infant morbidity. I have an NIH grant with Profs Wan (UCDMC) and Slupsky (FST) focused on methods to reduce liver cancer via suppression of intestinal dysbiosis and associated inflammation using supplemented milk oligosaccharides and bifidobacteria. As an initial part of that effort we have characterized the dysbiotic microbiota in the mouse model, noted a specific gender influence and showed how inflammation can be reversed by butyrate supplementation. Efforts employing milk oligosaccharides and bifidobacteria are ongoing but early results indicate successful suppression of inflammation driven by dysregulated bile acid synthesis in this mouse model. I have an ongoing collaboration with Prof Noratto (Texas A&M) focused on the impact of fiber supplementation on a mouse model of obesity. My lab has also worked on methods development for microbiota analysis. We were a testing lab site for the Microbiome Quality Control Project Consortium focused on evaluating variability in DNA extraction and library preparation in fecal microbiota analysis.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Boudry, G., M. K. Hamilton, M. Chichlowski, S. Wickramasinghe, D. Barile, K. M Kalanetra, D. A. Mills and H. E Raybould. Bovine milk oligosaccharides decrease gut permeability and improve inflammation and microbial dysbiosis in diet-induced obese mice. Journal of Dairy Science 100:2471-2481.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Davis, J., Z. Lewis, S. Krishnan, R. Bernstein, S. Moore, A. M. Prentice, D. A. Mills, C. B. Lebrilla, and A. Zivkovic. Growth and morbidity of Gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota. Nature Scientific Reports 7:40466.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Lewis, Z. T., K. Sidamonidze, V. Tsaturyan, D. Tsereteli, N. Khachidze, A. Pepoyan, E. Zhgenti, L. Tevzadze, A. Manvelyan, M. Balayan, P. Imnadze, T. Torok, D. G. Lemay, D. A. Mills. The fecal microbial community of breast-fed infants from Armenia and Georgia. Scientific Reports 7: 40932.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Smilowitz, J. T., D. G. Lemay, K. M. Kalanetra, E. L. Chin, A. M. Zivkovic, M. A. Breck, J. B. German, D. A. Mills, C. Slupsky and D. Barile. Tolerability and safety for the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults. Journal of Nutritional Science. 6:e6.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Hamilton, M. K., C. Ronveaux, B. M. Rust, J. W. Newman, M. Hawley, D. Barile, D. A. Mills and H. E. Raybould. Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability and microbial dysbiosis in high-fat fed mice. American Journal of Physiology - Gastrointestinal and Liver Physiology, 312(5): G474-G487.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Underwood, M. A., J. C. C. Davis, K. M. Kalanetra, S. Gehlot, S. Patole, D. J. Tancredi, D. A. Mills, C. B. Lebrilla, and K. Simmer. 2017. Digestion of human milk oligosaccharides by Bifidobacterium breve in the premature infant. Journal of Pediatric Gastroenterology & Nutrition 4:449-455.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Jena, P. K., L. Sheng, H. X. Liu, K. M. Kalanetra, A. Mirsoian, W. J. Murphy, S. W. French, V. V. Krishnan, D. A. Mills, Y.-J. Y. Wan. 2017. Western diet-induced dysbiosis in FXR knockout mice causes persistent hepatic inflammation post antibiotic treatment. American Journal of Pathology 187:1800-1813.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Sheng, L., P. K. Jena, H.-X. Liu, K. Kalanetra, F. Gonzalez, S. French, V. Krishnan, D. Mills, and Y.-J. Wan. Gender differences in bile acids and microbiota in relationship with gender dissimilarity in steatosis induced by diet and FXR inactivation. Scientific Reports 7: 1748.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Park, C., G. Xu, M. Barboza, I. M. Shah, H. Raybould, D. A. Mills and C. B. Lebrilla. Enterocyte glycosylation is responsive to changes in extracellular conditions: Implications for membrane functions. Glycobiology 27(9): 847860.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Garcia-Mazcorro, J. F., D. A. Mills, K. Murphy, G. Noratto. Effect of barley supplementation on the fecal microbiota, caecal biochemistry and key biomarkers of obesity and inflammation in obese db/db mice. European Journal of Nutrition DOI 10.1007/s00394-017-1523-y.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Mills, D. A. Probiotic nomenclature matters redux: confusion on Bifidobacterium longum subsp. infantis taxonomy persists. Current Medical Research and Opinion, 33(11): 2097.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Sinha, R., G. A.-Ali, E. Vogtmann, A. A. Fodor, B. Ren, A. Amir, E. Schwager, J. Crabtree, S. Ma, The Microbiome Quality Control Project Consortium (inc. D. A. Mills), C. C. Abnet, R. Knight, O. White, Curtis Huttenhower. The Microbiome Quality Control Project Baseline: Variation in microbial community amplicon sequencing. Nature Biotechnology 35:1077-1086.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Sheng, L., P. K. Jena, Y. Hu, H.-X. Liu, N. Nagar, K. M. Kalanetra, S. W. French, D. A. Mills, Y.-J. Wan. 2017. Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation. Journal of Pathology. 243:431-441.
  • Type: Book Chapters Status: Published Year Published: 2017 Citation: Lewis, Z. T. and D. A. Mills: Differential establishment of bifidobacteria in the breastfed infant gut, Isolauri, E., P. Sherman, and A. Walker, (ed), IN: Intestinal Microbiome: Functional Aspects in Health and Disease. Nestl� Nutr Inst Workshop Ser, vol 88, pp 149159, ( DOI: 10.1159/000455399 ), Nestec Ltd., Vevey/S. Karger AG, Basel.


Progress 10/01/15 to 09/30/16

Outputs
Target Audience:The main target audience for our microbial ecology work is the food, wine and biofuel industries. Our work on milk glycans/bifidobacteria/intestinal health is of great interest to the infant formula industry, the dairy industry and the pharmaceutical industry Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?In the last year I advised 3 scientific staff, 4 postdoctoral fellows, 5 PhD students, 2 MS students, and 10 undergraduate students. During this period some of my students presented their research at local and international meetings. How have the results been disseminated to communities of interest?In the past year I have presented my research at numerous commodity oriented meetings, national and international meetings. 1. "Human milk oligosaccharides -- Functional outcomes", 88th Nestlé Nutrition Institute Workshop, Playa del Carmen, Mexico, Sept. 25, 2016. 2. "Microbial landscapes within food production: A case for microbial terroir", FoodMicro 2016, Dublin, Ireland July 19-22, 2016. 3. "Establishment of a milk-oriented microbiota in infants: New insight into probiotics and prebiotics" Plenary Lecture, International Scientific Conference on Probiotics and Prebiotics, Budapest, Hungary, June 21-23, 2016. 4. "Establishment of a beneficial milk-oriented microbiota (MOM) in breast-fed infants: A naturally-evolved prebiotic enrichment". Divisional Lecture, American Society for Microbiology Annual Meeting, Boston, MA, June 17, 2016. 5. "Influence of the milk glycome on the developing neonate microbiota: Why babies cry over spilled milk" FASEB Meeting on Microbial Glycobiology, West Palm Beach, FL, June 14, 2016. 6. "The role of the milk glycome in the development of the infant gut microbiota: Why babies cry over spilled milk". Oxygen Club of California 2016 World Congress, Redox Medicine and Nutrition, Davis, CA May 4-6, 2016. What do you plan to do during the next reporting period to accomplish the goals?I will continue to do research and extension in the area of food microbiology. I will publish research, present seminars, train students and teach classes and short courses. I will also interface directly with stakeholders.

Impacts
What was accomplished under these goals? My research centers on the ecology, genetics and genomics of the microbes present in food and beverage fermentations or involved in intestinal health. Gut Health. Breast fed infants are typically colonized by bifidobacteria that are thought to protect, feed and communicate with the developing intestine. Understanding how human milk orchestrates this enrichment is critical to our comprehension of infant health and development but also provides a useful model for diet-based manipulation of the gut microbiota. Human milk contains a large amount of free and bound glycans thought to be involved in this bifidobacterial enrichment. My research has focused on deciphering the molecular mechanisms underlying this glycan-based enrichment as well as defining the molecular nature of bacterial-host interactions. In the past year we have continued to characterize the molecular nature of glycan consumption by neonate-borne gut microbiota--work that also involved various molecular and analytical methods development. This includes publications detailing: (1) Detailed characterization of milk oligosaccharide metabolism by Bifidobacterium longum and Bacteroides species; (2) Characterization of gut microbiota responses to milk oligosaccharide consumption as well as wheat and grain diets; (3) Methods to make ensure analytical integrity of fecal oligosaccharide and microbiome measurements; (4) Development of tools to characterize and validate commercial probiotic species; New methods to characterize metatranscriptomics; (5) Novel production methods to obtain the free oligosaccharides from bovine glycoproteins as well as methods to produce individual human milk oligosaccharides. We also published several reviews and a book chapter on milk oligosaccharide consumption. Food/Beverage Microbiology. During the period under review my lab used metagenomic tools to profile a range of foods and beverages and their processing environments. This includes publications detailing: grape and vine microbiota and their influence on wine metabolites and the ability of prion formation by Saccharomyces to impact the microbial ecology of wine fermentation. We also published a review on the microbial ecology of food and beverage production facilities.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Pudlo, N., K. Urs, S. S. Kumar, J. B. German, D. A. Mills and E. C. Martens. 2015. Symbiotic human gut bacteria with variable metabolic priorities for host mucosal glycans. mBio 6: e01282-15.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Sohn, K. K. Kalanetra, D. A. Mills and M. A. Underwood. 2016. Buccal administration of human colostrum: impact on the oral microbiota of premature infants. Journal of Perinatology 36:106111.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Powell, W.T., R. A. Borghese, K. M. Kalanetra, M. Mirmiran, D. A Mills, and M. A. Underwood. 2016. Probiotic administration in infants with gastroschisis. Journal of Pediatric Gastroenterology and Nutrition. 62:852-857.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Lewis, Z. T., G. Shani, C. Masarweh, M. Popovic, S. A. Frese, D. A. Sela, M. A. Underwood and D. A. Mills. 2016. Validating bifidobacterial species and subspecies identity in commercial probiotic products. Pediatrics Research 79: 445-452.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Hutkins, R., J. Krumbeck, L. B Bindels, P. Cani, G. Fahey, Jr, Y, Goh, B. Hamaker, E. Martens, D. A. Mills, R. Rastal, E. Vaughan. 2016. Prebiotics: why definitions matter. Current Opinion in Biotechnology 37:1-7.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Garcia-Mazcorro , J. F., I. Ivanov, D. A. Mills, G. Noratto . 2016. Influence of whole-wheat consumption on fecal microbial community structure of obese diabetic mice. PeerJ 4:e1702; DOI 10.7717/peerj.1702.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Dallas, D. C., F. Citerne, T. Tian, V. L. M. Silva, K. M. Kalanetra, S. A. Frese, R. C. Robinson, D. A. Mills and D. Barile. 2016. Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins. Food Chemistry 197: 273284.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Bokulich, N. A., Z. T. Lewis, K. L Boundy-Mills, D. A. Mills. 2016. A new perspective on microbial landscapes within food production. Current Opinion in Biotechnology 37:182189.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Charbonneau, M. R., D. ODonnell, L. V. Blanton, S. M. Totten, J. Davis, M. J. Barratt, J. Cheng, J. Guruge, M. Talcott, J. R. Bain, M. J. Muehlbauer, O. Ilkayeva, C. Wu, T. Struckmeyer, D. Barile, K. Maleta, K. Dewey, P. Ashorn, C. B. Newgard, C. Lebrilla, D. A. Mills, J. I. Gordon. 2016. Sialylated milk oligosaccharides promote growth in gnotobiotic mice and piglets harboring a stunted Malawian infant gut microbiota. Cell 164: 113.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Lewis, Z. T., J. Davis, J. T. Smilowitz, J B. German, C. B Lebrilla, D. A Mills. 2016. The impact of freeze-drying infant fecal samples on measures of their bacterial community profiles and milk-derived oligosaccharide content. PeerJ 4:e1612.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: 146. Chao Z., Y. Wu, H. Yu, I. M. Shah, Y. Li, J. Zeng, B. Liu, D. A. Mills and X. Chen. 2016. One-pot multienzyme (OPME) synthesis of human blood group H antigens and a human milk oligosaccharide (HMOS) with highly active Thermosynechococcus elongatus ?12-fucosyltransferase. Chemical Communications 52: 3899-3902.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Walker, G. A., A. Hjelmeland, N. A. Bokulich, D. A. Mills, S. E. Ebeler and L. F. Bisson. 2016. Impact of the [GAR+] prion on fermentation progression and bacterial population composition with Saccharomyces cerevisiae strain UCD932. American Journal of Enology and Viticulture. 67:296-307.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Karav, S., A. Le Parc, J. M. L. N. de Moura Bell, S. A. Frese1, N. Kirmiz, D. E. Block, D. Barile, and D. A. Mills. 2016. Oligosaccharides released from milk glycoproteins are selective growth substrates for infant-associated bifidobacteria. Applied and Environmental Microbiology 82:3622-3630.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Bokulich, N. A., C. Masarweh, T. S. Collins, G. Allen, H. Heymann, S. E. Ebeler and D. A. Mills. 2016. Associations among wine grape microbiome, metabolome, and fermentation behavior suggest microbial contribution to regional wine characteristics. mBio 7:e00631-16.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Charbonneau M. R., L. V. Blanton, D. B. DiGiulio, D. A. Relmam, Lebrilla CB, D. A. Mills and J. I. Gordon, 2016. A microbial perspective of human developmental biology. Nature 535:48-55.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: 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. 2016. Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial. Trials 17: 340.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Jeong KH, B. Israr, S. P. Shoemaker, D. A. Mills, J. Kim. 2016. Impact of lactic acid and hydrogen ion on the simultaneous fermentation of glucose and xylose by the carbon catabolite derepressed Lactobacillus brevis ATCC 14869. Journal of Microbiology and Biotechnology 26:1182-1189.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Garcia-Mazcorro, J., D. A. Mills, G. Noratto. 2016. Molecular exploration of fecal microbiome in quinoa-supplemented obese mice. FEMS Microbiology Ecology 92: fiw089.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Salcedo Domiguez, J., S. Frese, D. A. Mills and D. Barile. Characterization of porcine milk oligosaccharides during early lactation and their relation to the fecal microbiome. Journal of Dairy Science 99:7733-7743.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Davis, J. C.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. 2016. Identification of oligosaccharides in feces of breast-fed infants and their correlation with the gut microbial community. Molecular and Cellular Proteomics 15:2987-3002.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Garrido, D., S. Ruiz-Moyano, N. Kirmiz, J. C. C. Davis, S. Totten, D. G. Lemay, J. A. Ugalde, J. B. German, C. B. Lebrilla, and D. A. Mills. 2016. A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596. Nature Scientific Reports. 6:35045.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Westreich, S. T., I. Korf, D. A. Mills, DG Lemay. SAMSA: A comprehensive metatranscriptome analysis pipeline. 2016. BMC Bioinformatics 17:399.
  • Type: Book Chapters Status: Published Year Published: 2016 Citation: Kirmiz, N. and D. A. Mills. 2016. Intestinal microbiota in breast-fed infants: insights into infant-associated bifidobacteria and human milk glycans. In Watson, R. and V. R. Preedy Eds. Bioactive Foods in Promoting Health: Probiotics, Prebiotics, and Synbiotics 2nd Edition. Elsevier, New York, New York.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Karav, S., J. M. L. N. de Moura Bell, A. Le Parc, Y. Liu, D. A. Mills, D. E. Block and D. Barile. 2015. Characterizing the release of bioactive N-glycans from dairy products by a novel endo-?-N-acetylglucosaminidase. Biotechnology Progress 31:1331-1339.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Le Parc, A., S. Karav, J. M. L. N. de Moura Bell, A. Le Parc, Y. Liu, D. A. Mills, D. E. Block and D. Barile. 2015. A novel endo-?-N-acetylglucosaminidase releases specific N-glycans depending on different reaction conditions. Biotechnology Progress 31:1323-1330.


Progress 11/06/14 to 09/30/15

Outputs
Target Audience:The main target audience for our microbial ecology work is the food, wine and biofuel industries. Our work on milk glycans/bifidobacteria/intestinal health is of great interest to the infant formula industry, the dairy industry and the pharmaceutical industry. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?In the last five years I advised 3 scientific staff, 2 postdoctoral fellows, 3 PhD students, 2 MS students, and 16 undergraduate students. During this period some of my students presented their research at local and international meetings. How have the results been disseminated to communities of interest?In the past year I have presented my research at numerous commodity oriented meetings, national and international meetings as well as meeting directly with a larger number of companies. Presentations 2015. 1. "A regional character in the microbes associated with wine production", Vintage Report Conference 2016, Napa, CA January 19, 20-16. 2. "Human milk as a model for nutrition and manipulation of the gut microbiota" 11th Latin American Symposium on Food Science, Campinas, Brazil, Nov 11, 2015. 3. "Use of next generation sequencing to profile whole food facility microbiota changes" 11th Latin American Symposium on Food Science, Campinas, Brazil, Nov 10, 2015. 4. "When good milk goes bad: Can milk glycans create gut dysbiosis?" UC Davis Research Retreat on Host-Microbe Interactions, Granlibakken Conference Center, Tahoe City, CA, Nov 6, 2015. 5. "Influence of the milk glycome on the developing neonate microbiota: Why babies cry Over spilled milk". 2nd Annual Microbiome Symposium, University of Pennsylvania Microbiome Program, Philadelphia, PA, Oct 29, 2015. 6. "Microbial landscapes within food production: A case for microbial terroir", Joint Genome Institute, Walnut Creek, CA Oct 22, 2015. 7. "The role of the milk glycome in the development of the infant gut microbiota: Why babies cry over spilled milk". UC Davis Center for Mind & Brain Summit Series, Davis, CA Oct 16, 2015. 8. "Microbial landscapes within wine production--new tools and new ideas", Department of Viticulture and Enology, Fresno State University, Fresno, CA, Sept 30, 2015 9. "A milk-oriented microbiota in breast fed infants: a glycan-driven microbial enrichment", 23rd International Symposium on Glycoconjugates, Split, Croatia, Sept 19, 2015. 10. "Yeast and bacterial landscapes within food production: A case for microbial terroir." International Specialized Symposium on Yeast, Perugia, Italy, Sept 15, 2015. 11. "Microbial landscapes within wine production: Evidence for a microbial link to the regional character in wines?" MicroWine Kick-off Meeting Rungsted, Denmark, Sept 8, 2015. 12. "A milk-oriented microbiota (MOM) in infants: How HMO help babies find their 'other' MOM". FASEB Meeting on The Origins and Benefits of Biologically Active Components in Human Milk. Big Sky, MT, July 19, 2015. 13. "Diet, milk and the gut microbiota of the young". The Human Microbiome: Present Status and Future Prospects, B-DEBATE, International Center for Scientific Debate, Barcelona, Spain. July 1, 2015. 14. "Microbial landscapes in wine production: Evidence for a microbial link to regional character in wines". 10th International Symposium on Oenology of Bordeaux, Palais de la Bourse, Bordeaux, France, June 31, 2015. 15. "A Milk-Oriented Microbiota (MOM) in Nursing Infants: What MOMs can teach us about next generation prebiotics and probiotics". Annual Meeting of Korean Society for Food Science and Technology, Busan, Korea, June 3, 2015 16. "A Milk-Oriented Microbiota (MOM) in Nursing Infants: What MOMs can teach us about next generation prebiotics and probiotics". 2015 International Symposium: Recent Breakthroughs in Omics Research for Food-borne Pathogens Seoul National University, Seoul, Korea, June 2, 2015. 17. "Select probiotics prevent pathogen growth driven by commensal glycan degradation--Probiotic Assisted Colonization Resistance". "Hot-Topics" International Scientific Association for Prebiotics and Probiotics. May 19, 2015. 18. "A Milk-Oriented Microbiota (MOM) in nursing infants: What MOMs can teach us about next generation prebiotics and probiotics.". Frontiers of Lactic Acid Bacteria, Bioprocessing and Health Symposium, North Carolina State University, Raleigh, NC, May 15, 2015. 19. "Microbial landscapes within food and beverage production", Research on Future of Food, Institute for the Future Retreat, San Francisco, CA. May 6, 2015. 20. "Microbial landscapes within wine and beer production". Joint BioEnergy Institute, Emeryville, CA April 29th. 21. "Microbial ecology of wineries: An update". Diageo Winemakers meeting. UC Davis, April 23, 2015 22. "A new era in wine microbiology-routine tracking of all microbes in all places". Plant and Microbial Biology Department, University of California, Berkeley, CA, April 22, 2015. 23. "Microbial landscapes within food production: A case for microbial terroir". Department of Plant Pathology, UC Davis April 20th. 24. "The influence of the milk glycome on the developing neonate microbiota". Department of Bacteriology. University of Wisconsin, Madison, WI, April 9, 2015. 25. "A Milk-Oriented Microbiota (MOM) in infants: Lessons from your other MOM". Annual Meeting of the American Society for Biochemistry and Molecular Biology. Boston, MA, March 28, 2015. 26. "Assemblage of a Milk-oriented Microbiota (MOM) in infants: Lessons from your other MOM." Annual Meeting of the Human Biology Association, St. Louis, MO, March 25-26. 27. "The influence of the milk glycome on the developing infant microbiota". 4th Beneficial Microbes Conference. The Hague, the Netherlands, March 16-18, 2015. 28. "Influence of the milk glycome on the developing neonate microbiota". Gut Microbiota for Health: World Summit. Barcelona, Spain, March 14-15, 2015. 29. "The influence of the milk glycome on the developing infant microbiota". Department of Pathology, UC Davis Medical School, February 25, 2015. 30. "A new era in wine microbiology-routine tracking of all microbes in all places". UC Davis Viticulture and Enology On-the-road in the Foothills, Plymouth, CA, February 27, 2015 31. "The future of food, agriculture and wellness" Research Panel at UC Davis Investment Forum on Food Agricuture and Wellness. University of California, Davis, CA Jan 23, 2015. 32. "The genius of milk--Natures first functional food". Exploratorium, San Francisco, CA, Jan 8, 2015. What do you plan to do during the next reporting period to accomplish the goals?I will continue to do research and extension in the area of food microbiology. I will publish research, present seminars, train students and teach classes and short courses. I will also interface directly with stakeholders.

Impacts
What was accomplished under these goals? My research centers on the ecology, genetics and genomics of the microbes present in food and beverage fermentations or involved in intestinal health. Food/Beverage Microbiology. During the period under review my lab used novel metagenomic tools to profile a range of foods and beverages and their processing environments. This includes publications detailing: grape and vine microbiota, the regionality of fermented Matsoon from Armenia and Georgia, a comprehensive analysis of a brewery microbiota and an examination of the microbiota associated with cheese spoilage. Gut Health. Breast fed infants are typically colonized by bifidobacteria that are thought to protect, feed and communicate with the developing intestine. Understanding how human milk orchestrates this enrichment is critical to our comprehension of infant health and development but also provides a useful model for diet-based manipulation of the gut microbiota. Human milk contains a large amount of free and bound glycans thought to be involved in this bifidobacterial enrichment. My research has focused on deciphering the molecular mechanisms underlying this glycan-based enrichment as well as defining the molecular nature of bacterial-host interactions. In the past year we have continued to characterize the molecular nature of glycan consumption by infant-borne bifidobacteria--work that also involved various molecular and analytical methods development. This includes publications detailing: the transcriptional response of Bifidobacterium infantis and Bifidobacterium bifidum to growth on milk sugars, the influence of mothers secretor status on infant bifidobacterial enrichment, an assessment of pig neonatal microbiome development, an analysis of a novel endoglycosidase for removing glycans from milk glycoproteins and the influence of milk glycan grown bifidobacteria on intestinal cell responses.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Bokulich, N. A., L. Amiranashvili, K. Chitchyan, N. Ghazanchyan, K. Darbinyan, N. Gagelidze, T. Sadunishvili, V. Goginyan, G. Kvesitadze, T. Torok and D. A. Mills. 2015. Microbial biogeography of the transnational fermented milk Matsoni. Food Microbiology 50:1219.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Zarraonaindia, I., S. M. Owens, K. West, J. Hampton-Marcell, S.Lax, N. A. Bokulich, D. A. Mills, G Martin, S. Taghavid, D. van der Lelie and J. A. Gilbert. 2015. The soil microbiome influences grapevine-associated microbiota. mBio 6:e02527-14
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Porcellato, D., M. E. Johnson. K. Houck. S. B. Skeie. D. A. Mills. K. M. Kalanetra, J. L. Steele. 2015. Potential of Lactobacillus curvatus LFC1 to produce slits in Cheddar cheese. Food Microbiology 49: 6573.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Subramanian, S., L. Blanton, S. A. Frese, M. Charbonneau, D. A. Mills, and J. I. Gordon. 2015. Cultivating healthy growth and nutrition through the gut microbiota. Cell 161:36-48.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Frese, S. A. and D. A. Mills. 2015. Birth of the infant gut microbiome: Moms deliver twice! Cell Host and Microbe 17:543544.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: 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. 2015. Maternal fucosyltransferase 2 status impacts gut bifidobacterial communities of breastfed infants. Microbiome 3:13.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Bokulich, N. A., J. Bergsveinson, B. Ziola, D. A. Mills. 2015. Mapping microbial ecosystems and spoilage-gene flow in brewery environments highlights patterns of contamination and resistance. Elife 4:e04634.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Kim, S. R., T. V. Nguyen, N. R. Seo, S. Jung, H. J. An, D. A. Mills, and J.-H. Kim. 2015. Comparative proteomics: assessment of biological variability and dataset comparability. BMC Bioinformatics. 16:121.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Frese, S. and D. A. Mills. 2015. Should infants cry over spilled milk? Fecal glycomics as an indicator of a healthy infant gut microbiome. Journal of Pediatric Gastroenterology and Nutrition 60:695.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Garrido, D. S. Ruiz-Moyano, D. G. Lemay, D. A. Sela, J B. German and D. A Mills. 2015. Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Nature Scientific Reports 5:13517.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Karav, S., A. Le Parc-Le Bouedec, J. M. L. N. de Moura Bell, C. Rouqui�, D. A. Mills, D. Barile and D. E. Block. 2015. Kinetic characterization of a novel endo-?-N-acetylglucosaminidase on concentrated bovine colostrum whey to release bioactive glycans. Enzyme and Microbial Technology 77:4653.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Swadener, M. L. and D. A. Mills. 2015. A new look at an old practice: How SO2 additions influence microbial diversity during fermentation. Wine & Viticulture Journal 3:32-34.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Frese, SA, K, Parker, C. C. Calvert and D. A. Mlls. 2015. Diet shapes the microbiome of pigs during nursing and weaning. Microbiome 3:28.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Wickramasinghe, S, A. R. Pacheco, D. G. Lemay, and D. A. Mills. 2015. Bifidobacteria grown in human milk oligosaccharides down regulate the expression of inflammation-related genes in Caco-2 cells. BMC Microbiology 15:172.