Progress on the molecular mechanism and probiotic effect of B. longum subsp. infantis subspecies using HMOs

Abstract

Abstract: Abstract: Human milk is the most important source of nutrition in early infancy which can meet all the nutritional needs in the first 6 months of birth, and it also contains many bioactive substances that can regulate the intestinal flora, promote the development of the immune system, and enhance the intestinal barrier. Human milk oligosaccharides (HMOs) are one of the active substances in human milk. They cannot be directly digested and absorbed by infants but can be used as a prebiotic to stimulate the establishment and evolution of intestinal flora. The Bifidobacterium longum subsp. infantis is the dominant microorganism in the gut of breastfed infants, which has almost all the gene clusters required for metabolizing the main HMOs, and its interaction with HMOs plays a key role in early infant intestinal health. This review summarizes the composition and structure of HMOs, describes the way B. longum subsp. infantis utilizes HMOs, and summarizes the probiotic effects of B. longum subsp. infantis metabolizing HMOs in infants.

Key words: Human milk oligosaccharides, B. longum subsp. infantis, Metabolites, Utilization mechanism, probiotic function

CLC Number:

Yu-Han CHEN Li QiaoHui Li Yan Su Qian Huanxin GUO Bo-Fan DUAN [中]孟祥晨 [英]MENG Xiang-Chen. Progress on the molecular mechanism and probiotic effect of B. longum subsp. infantis subspecies using HMOs[J]. FOOD SCIENCE, 0, (): 0-0.

References

[1]ZHANG Bin, LI Longqing, LIU Feitong, et al. Human milk oligosaccharides and infant gut microbiota: Molecular structures, utilization strategies and immune function [J]. Carbohydrate Polymers, 2022, 276: 118738. DOI: 10.1016/j.carbpol.2021.118738.
[2]LE DOARE K, HOLDER B, Bassett A, et al. Mother's milk: A purposeful contribution to the development of the infant microbiota and immunity [J]. Frontiers in Immunology, 2018, 9:361. DOI: 10.3389/fimmu.2018.00361.
[3]HILL D R, NEWBURG D S. Clinical applications of bioactive milk components [J]. Nutrition Reviews, 2015, 73(7): 463-76. DOI: 10.1093/nutrit/nuv009.
[4]VASS R A, KEMENY A, DERGEZ T, et al. Distribution of bioactive factors in human milk samples [J]. International Breastfeeding Journal, 2019, 14(9). DOI: 10.1186/s13006-019-0203-3.
[5]GRANGER C L, EMBLETON N D, Palmer J M, et al. Maternal breastmilk, infant gut microbiome and the impact on preterm infant health [J]. Acta Paediatrica, 2021, 110(2): 450-7. DOI: 10.1111/apa.15534.
[6]GILA-DIAZ A, ARRIBAS S M, ALGARA A, et al. A review of bioactive factors in human breastmilk: A focus on prematurity [J]. Nutrients, 2019, 11(6) :1307. https://doi.org/10.3390/nu11061307.
[7]AUSTIN S, DE CASTRO C A, SPRENGER N, et al. Human milk oligosaccharides in the milk of mothers delivering term versus preterm infants [J]. Nutrients, 2019, 11(6) :1282. https://doi.org/10.3390/nu11061282.
[8] KONG, Chunli, ELDERMAN M, CHENG, Lianghui, et al. Modulation of intestinal epithelial glycocalyx development by human milk oligosaccharides and non-digestible carbohydrates [J]. Molecular Nutrition & Food Research, 2019, 63(17). DOI: 10.1002/mnfr.201900303.
[9]HE Y, LIU S, LEONE S, et al. Human colostrum oligosaccharides modulate major immunologic pathways of immature human intestine [J]. Mucosal Immunology, 2014, 7(6): 1326-39. DOI: 10.1038/mi.2014.20.
[10]QUIGLEY M A, CARSON C, SACKER A, et al. Exclusive breastfeeding duration and infant infection [J]. European Journal of Clinical Nutrition, 2016, 70(12): 1420-7. DOI: 10.1038/ejcn.2016.135.
[11]SAKANAKA M, GOTOH A, YOSHIDA K, et al. Varied pathways of infant gut-associated bifidobacterium to assimilate human milk oligosaccharides: Prevalence of the gene set and its correlation with bifidobacteria-rich microbiota formation [J]. Nutrients, 2020, 12(1):71. https://doi.org/10.3390/nu12010071.
[12]MASI A C, STEWART C J. Untangling human milk oligosaccharides and infant gut microbiome [J]. Iscience, 2022, 25(1). DOI: 10.1016/j.isci.2021.103542.
[13]THONGARAM T, HOEFLINGER J L, CHOW J, et al. Human milk oligosaccharide consumption by probiotic and human-associated bifidobacteria and lactobacilli [J]. Journal of Dairy Science, 2017, 100(10): 7825-33. DOI: 10.3168/jds.2017-12753.
[14]LOCASCIO R G, DESAI P, SELA D A, et al. Broad conservation of milk utilization genes in Bifidobacterium longum subsp infantis as revealed by comparative genomic hybridization [J]. Applied and Environmental Microbiology, 2010, 76(22): 7373-81. DOI: 10.1128/aem.00675-10.
[15]KATAYAMA T. Host-derived glycans serve as selected nutrients for the gut microbe: human milk oligosaccharides and bifidobacteria [J]. Bioscience Biotechnology and Biochemistry, 2016, 80(4): 621-32. DOI: 10.1080/09168451.2015.1132153.
[16]BODE L. Human milk oligosaccharides: Next-generation functions and questions [J]. Nestle Nutrition Institute workshop series, 2019, 90: 191-201. DOI: 10.1159/000490306.
[17]THURL S, MUNZERT M, HENKER J, et al. Variation of human milk oligosaccharides in relation to milk groups and lactational periods [J]. British Journal of Nutrition, 2010, 104(9): 1261-71. DOI: 10.1017/s0007114510002072.
[18]EWALD D R, SUMNER S C J. Human microbiota, blood group antigens, and disease [J]. Wiley Interdisciplinary Reviews-Systems Biology and Medicine, 2018, 10(3). DOI: 10.1002/wsbm.1413.
[19]URASHIMA T, ASAKUMA S, Leo F, et al. The Predominance of type I oligosaccharides is a feature specific to human breast milk [J]. Advances in Nutrition, 2012, 3(3): 473S-82S. DOI: 10.3945/an.111.001412.
[20] CHENG Lianghui, AKKERMAN R, KONG ChunLi, et al. More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects [J]. Critical Reviews in Food Science and Nutrition, 2021, 61(7): 1184-200. DOI: 10.1080/10408398.2020.1754756.
[21]VAN LEEUWEN S S. Challenges and pitfalls in human milk oligosaccharide analysis [J]. Nutrients, 2019, 11(11):2684. DOI: 10.3390/nu11112684.
[22]TONON K M, MIRANDA A, ABR?O A C F V, et al. Validation and application of a method for the simultaneous absolute quantification of 16 neutral and acidic human milk oligosaccharides by graphitized carbon liquid chromatography–electrospray ionization – mass spectrometry [J]. Food Chemistry, 2019, 274: 691-7. DOI: 10.1016/j.foodchem.2018.09.036.
[23] HUANG Chuncui, SUN Shiwei, YAN Jingyu, et al. Identification of carbohydrate peripheral epitopes are important for recognition by positive-ion MALDI multistage mass spectrometry [J]. Carbohydrate Polymers, 2020, 229:115528. DOI: 10.1016/j.carbpol.2019.115528.
[24]SHI Qi, YAN Jingyu JIANG Bin, et al. A general strategy for the structural determination of carbohydrates by multi-dimensional NMR spectroscopies [J]. Carbohydrate Polymers, 2021, 267: 118218. DOI: 10.1016/j.carbpol.2021.118218.
[25]SELA D A, GARRIDO D, LERNO L, et al. Bifidobacterium longum subsp infantis ATCC 15697 alpha-fucosidases are active on fucosylated human milk oligosaccharides [J]. Applied and Environmental Microbiology, 2012, 78(3): 795-803. DOI: 10.1128/aem.06762-11.
[26]SELA D A, LI Y H, LERNO L, et al. An infant-associated bacterial commensal utilizes breast milk sialyloligosaccharides [J]. Journal of Biological Chemistry, 2011, 286(14) :P11909-11918. DOI: 10.1074/jbc.m110.193359.
[27]YOSHIDA E, SAKURAMA H, KIYOHARA M, et al. Bifidobacterium longum subsp. infantis uses two different β-galactosidases for selectively degrading type-1 and type-2 human milk oligosaccharides [J]. Glycobiology, 2011, 22(3): 361-8. Bifidobacterium longum subsp. infantis uses two different β-galactosidases for selectively degrading type-1 and type-2 human milk oligosaccharides.
[28]GARRIDO D, RUIZ-MOYANO S, MILLS D A. Release and utilization of N-acetyl-D-glucosamine from human milk oligosaccharides by Bifidobacterium longum subsp infantis [J]. Anaerobe, 2012, 18(4): 430-5. DOI: 10.1016/j.anaerobe.2012.04.012.
[29]SAKANAKA M, HANSEN M E, GOTOH A, et al. Evolutionary adaptation in fucosyllactose uptake systems supports bifidobacteria-infant symbiosis [J]. Science Advances, 2019, 5(8) :eaaw7696. DOI: 10.1126/sciadv.aaw7696.
[30]SELA D A, CHAPMAN J, ADEUYA A, et al. The genome sequence of Bifidobacterium longum subsp infantis reveals adaptations for milk utilization within the infant microbiome [J]. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(48): 18964-9. DOI: 10.1073/pnas.0809584105.
[31]GARRIDO D, RUIZ-MOYANO S, JIMENEZ-ESPINOZA R, et al. Utilization of galactooligosaccharides by Bifidobacterium longum subsp infantis isolates [J]. Food Microbiology, 2013, 33(2): 262-70. DOI: 10.1016/j.fm.2012.10.003.
[32]李明洁. 长双歧杆菌婴儿亚种的功能基因组及其对DSS诱导的结肠炎的影响研究 [D]; 江南大学, 2022. DOI:10.27169/d.cnki.gwqgu.2022.001892.
[33]NAGAE M, TSUCHIYA A, KATAYAMA T, et al. Structural Basis of the Catalytic Reaction Mechanism of Novel 1,2-α-L-fucosidase from Bifidobacterium bifidum [J]. Journal of Biological Chemistry, 2007, 282(25): 18497-509. DOI: 10.1074/jbc.m702246200.
[34]ASAKUMA S, HATAKEYAMA E, URASHIMA T, et al. Physiology of consumption of human milk oligosaccharides by infant gut-associated bifidobacteria [J]. Journal of Biological Chemistry, 2011, 286(40): 34583-92. DOI: 10.1074/jbc.m111.248138.
[35]SALLI K, HIRVONEN J, SIITONEN J, et al. Selective utilization of the human milk oligosaccharides 2 '-fucosyllactose, 3-fucosyllactose, and difucosyllactose by various probiotic and pathogenic bacteria [J]. Journal of Agricultural and Food Chemistry, 2021, 69(1): 170-82. DOI: 10.1021/acs.jafc.0c06041.
[36]JAMES K, MOTHERWAY M O, BOTTACINI F, et al. Bifidobacterium breve UCC2003 metabolises the human milk oligosaccharides lacto-N-tetraose and lacto-N-neo-tetraose through overlapping, yet distinct pathways [J]. Scientific Reports, 2016, 6(1):38560. DOI: 10.1038/srep38560.
[37]KITAOKA M, TIAN J S, NISHIMOTO M. Novel putative galactose operon involving lacto-N-biose phosphorylase in Bifidobacterium longum [J]. Applied and Environmental Microbiology, 2005, 71(6): 3158-62. DOI: 10.1128/aem.71.6.3158-3162.2005.
[38]RODRíGUEZ-DíAZ J, MONEDERO V, YEBRA MARíA J. Utilization of natural fucosylated oligosaccharides by three novel α-l-Fucosidases from a probiotic lactobacillus casei strain [J]. Applied and Environmental Microbiology, 2011, 77(2): 703-5. DOI: 10.1128/aem.01906-10.
[39]GARRIDO D, RUIZ-MOYANO S, LEMAY D G, et al. Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria [J]. Scientific Reports, 2015, 5(1): 13517. DOI: 10.1038/srep13517.
[40]WARD R E, NINONUEVO M, MILLS D A, et al. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri [J]. Applied and Environmental Microbiology, 2006, 72(6): 4497-9. DOI: 10.1128/aem.02515-05.
[41]SAKURAMA H, KIYOHARA M, WADA J, et al. Lacto-N-biosidase Encoded by a Novel Gene of Bifidobacterium longum Subspecies longum shows unique substrate specificity and requires a designated chaperone for its active expression [J]. Journal of Biological Chemistry, 2013, 288(35): 25194-206. DOI: 10.1074/jbc.m113.484733.
[42]FUJITA K, OURA F, NAGAMINE N, et al. Identification and molecular cloning of a novel glycoside hydrolase family of core 1 type O-glycan-specific endo-α-N-acetylgalactosaminidase from Bifidobacterium longum [J]. Journal of Biological Chemistry, 2005, 280(45): 37415-22. DOI: 10.1074/jbc.m506874200.
[43]GARRIDO D, RUIZ-MOYANO S, KIRMIZ N, et al. A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp longum SC596 [J]. Scientific Reports, 2016, 6:35045. DOI: 10.1038/srep35045.
[44]MATSUKI T, YAHAGI K, MORI H, et al. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development [J]. Nature Communications, 2016, 7:11939. DOI: 10.1038/ncomms11939.
[45]KIM J H, AN H J, GARRIDO D, et al. Proteomic Analysis of Bifidobacterium longum subsp infantis Reveals the Metabolic Insight on Consumption of Prebiotics and Host Glycans [J]. Plos One, 2013, 8(2) :e57535. DOI: 10.1371/journal.pone.0057535.
[46]LAWSON MAE, O’NEILL I J, KUJAWSKA M, et al. Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem [J]. Isme Journal, 2020, 14(2): 635-48. DOI: 10.1038/s41396-019-0553-2.
[47]ZUURVELD M, VAN WITZENBURG N P, GARSSEN J, et al. Immunomodulation by human milk oligosaccharides: The potential role in prevention of allergic diseases [J]. Frontiers in Immunology, 2020, 11:801. DOI: 10.3389/fimmu.2020.00801.
[48]ALESSANDRI G, OSSIPRANDI M C, MACSHARRY J, et al. Bifidobacterial dialogue with its human host and consequent modulation of the immune system [J]. Frontiers in Immunology, 2019, 10:2348-. DOI: 10.3389/fimmu.2019.02348.
[49]FUKUDA S, TOH H, HASE K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate [J]. Nature, 2011, 469(7331): 543-U791. DOI: 10.1038/nature09646.
[50]RIOS-COVIAN D, RUAS-MADIEDO P, MARGOLLES A, et al. Intestinal short chain fatty acids and their link with diet and human health [J]. Frontiers in Microbiology, 2016, 7:185. DOI: 10.3389/fmicb.2016.00185.
[51]任昕淼, 肖梦诗, 南世豪, 等.岩藻糖基化胞外多糖降解产物对婴儿肠道菌群的影响[J/OL].食品科学:1-14[2023-05-19].http://kns.cnki.net/kcms/detail/11.2206.TS.20221229.2000.023.html.
[52]PERDIJK O, VAN BAARLEN P, FERNANDEZ-GUTIERREZ M M, et al. Sialyllactose and galactooligosaccharides promote epithelial barrier functioning and distinctly modulate microbiota composition and short chain fatty acid production in vitro [J]. Frontiers in Immunology, 2019, 10(94). DOI: 10.3389/fimmu.2019.00094.
[53]FRESE S A, HUTTON A A, CONTRERAS L N, et al. Persistence of supplemented Bifidobacterium longum subsp. infantis EVC001 in breastfed infants [J]. Msphere, 2017, 2(6). DOI: 10.1128/msphere.00501-17.
[54]LAURSEN M F, SAKANAKA M, VON BURG N, et al. Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut [J]. Nature Microbiology, 2021, 6(11): 1367-82. DOI: 10.1038/s41564-021-00970-4.
[55]邓小玉, 王颖熠, 党倩倩, 等. 肠道菌群及代谢产物对免疫抑制剂抗肿瘤疗效的研究进展 [J]. 中国现代医生, 2022, 60(31): 131-5.
[56]EHRLICH A M, PACHECO A R, HENRICK B M, et al. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells [J]. Bmc Microbiology, 2020, 20(1):357. DOI: 10.1186/s12866-020-02023-y.
[57]HENRICK B M, RODRIGUEZ L, LAKSHMIKANTH T, et al. Bifidobacteria-mediated immune system imprinting early in life [J]. Cell, 2021, 184(15): 3884-+. DOI: 10.1016/j.cell.2021.05.030.
[58]LIN Chunxiu, LIN Yugui, ZHANG Heng, et al. Intestinal 'infant-type' bifidobacteria mediate immune system development in the first 1000 days of life [J]. Nutrients, 2022, 14(7) : 1498. DOI: 10.3390/nu14071498.
[59]DEDON L R, ?ZCAN E, RANI A, et al. Bifidobacterium infantis metabolizes 2′fucosyllactose-derived and free fucose through a common catabolic pathway resulting in 1,2-propanediol secretion [J]. Frontiers in Nutrition, 2020, 7:583397. DOI: 10.3389/fnut.2020.583397.
[60]O'BRIEN C E, MEIER A K, CERNIOGLO K, et al. Early probiotic supplementation with B. infantis in breastfed infants leads to persistent colonization at 1 year [J]. Pediatric Research, 2022, 91(3): 627-36. DOI: 10.1038/s41390-020-01350-0.
[61]胡世莲, 方向. 肠道菌群与免疫的研究进展 [J]. 中国临床保健杂志, 2021, 24(03): 294-300.
[62]CHICHLOWSKI M, DE LARTIGUE G, GERMAN J B, et al. Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function [J]. Journal of Pediatric Gastroenterology and Nutrition, 2012, 55(3): 321-7. DOI: 10.1097/mpg.0b013e31824fb899.
[63]WICKRAMASINGHE S, PACHECO A R, LEMAY D G, et al. Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells [J]. Bmc Microbiology, 2015, 15:172. DOI: 10.1186/s12866-015-0508-3.
[64]HUDA M N, AHMAD S M, ALAM M J, et al. Bifidobacterium abundance in early infancy and vaccine response at 2 years of age [J]. Pediatrics, 2019, 143(2): e20181489. DOI: 10.1542/peds.2018-1489.
[65]RAMANI S, STEWART C J, LAUCIRICA D R, et al. Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection [J]. Nature Communications, 2018, 9(1) : 5010. DOI: 10.1038/s41467-018-07476-4.
[66]MASI A C, EMBLETON N D, LAMB C A, et al. Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis [J]. Gut, 2021, 70(12): 2273-+. DOI: 10.1136/gutjnl-2020-322771.
[67]UNDERWOOD M A, ARRIOLA J, GERBER C W, et al. Bifidobacterium longum subsp infantis in experimental necrotizing enterocolitis: alterations in inflammation, innate immune response, and the microbiota [J]. Pediatric Research, 2014, 76(4): 326-33. DOI: 10.1038/pr.2014.102.
[68]SEPPO A E, BU K, JUMABAEVA M, et al. Infant gut microbiome is enriched with Bifidobacterium longum ssp. infantis in Old Order Mennonites with traditional farming lifestyle [J]. Allergy, 2021, 76(11): 3489-503. DOI: 10.1111/all.14877.
[69]BYCH K, MIKS M H, JOHANSON T, et al. Production of HMOs using microbial hosts - from cell engineering to large-scale production [J]. Current Opinion in Biotechnology, 2019, 56: 130-7. DOI: 10.1016/j.copbio.2018.11.003.