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Chapter 16 Bifidobacterium longum EMM. Quigley ‘bynda Kad David M Underwood Centr fr Digestive Diorder, Houston Methodist Hospital and Well Cornel Mecica! College, Houston, TX, United Sates ‘The species of Bifidobacteria now referred to as Bifdabac- 4erium longum contains three subspecies: longum, infantis, ‘and suis which were originally categorized as separate: ‘species. Subsequent analyses of their sequences revealed ‘high degree of homology leading to their inclusion un- der one species, B. longum [1,2]. AS B. longum spp. suis is ound in the porcine intestine and has not been explored for ‘probiotic properties in man, it will not be considered fur- ther. B. longum spp. infantis and longum have been isolated {from the infant and adult intestine and several strains from. ‘both subspecies have been studied in the laboratory, as well ‘as in clinical tials as probiotics [4]. Indeed, B. fongum ‘trains are typically dominant in the breast-fed infant gut [4]. One such strain, B. longum spp. infantis 35624, has al- ready been the subject of a separate chapter and will not be discussed further here. Several other fongum sisans will be discussed: B. longum bbS36; B, dongum es 1; B. longum ‘wIL; B. longum NCC 3001; B. longum 1714; B. fongum KACC 91563; B. longum spp. longum SPM 1208, 1206, 1207; B. longum subsp. infantis ATCC 15697. as fas been ‘emphasized earlier and in the introductory section on Bi- fidobacteria as probiotics, there is considerable homology between these strains and, as their complete genomes are ascribed, iis likely that some strains well be reclassified ‘and renamed [5,6]. A name change does not, of course im- ply a change of properties or function; it merely provides a ‘more precise taxonomy. It is important, therefore that the: reader remain vigilant for name changes among Bifdobac- ‘teria, especially in the species B. longum. (CHARACTERIZATION AND LABORATORY STUDIES ‘The entire genome sequence and plasmids of a number of {B. longum strains have been described [7-9]. Such studies ‘re valuable, not only in predicting likely biological actions, ‘but also safety, Thus, Wel and coworkers, in sequencing, ‘TMi Cnet Pigg Sryagtesot acne Ateneo 'B. longum JDMBO1, identified 36 genes associated with ‘antibiotic resistance, $ enzymes related to harmful me- tabolites, and 162 nonspecific virulence factors mainly associated with transcriptional regulation, adhesion, and ‘sugar and amino acid transport. Of greatest concern was a ‘gene conferring resistance to tetracycline that was capable Of transfer [10]. Their work highlights the importance of ‘knowing your probiotic at genome level; a strategy increas- ingly adopted by those who work in this field and strive to develop high quality products. Additional information on the potential effects of strains has also been gained from studies involving proteomics and transcriptomics {11,12 ‘Supporting their ability to survive transit through the in- testing, strains of 8. longum are bile resistant and many produce a well-defined exopolysaccharide coal that may be felevant to biological effects [13,14]. Interestingly, some differences in cell surface properties have been identified between strains isolated from preterm and term infants sug- gesting an adaptation to differing environments [15]. {In vito and in vivo animal studies have identified ‘a number of properties of potential clinical importance ‘among B. longum strains. These have included antiviral [16.17], metabotic [18], antioxidant (19), immunomodala- tory {20-26}, and neuromodulatory [27~79} effects, as well ‘as potentially beneficial impacts on the systemic circulation [30], intestinal transport [31 and the gut barier [32-14 CLINICAL STUDIES Given that some of the laboratory studies described earlier ‘were performed in animal models of human disease, suchas, colitis (33), cliae disease |72|. food and systemic alley [23,24], necrotizing enterocolitis [26], and Salmoneltaintec- tion [25], it should come as no surprise that efficacy has also been evaluated and defined ina number of clinical situations ‘and disease states. Fist, B. longum strains have been shown to exert antiinflammatory effects in the elderly (MM-2) 139 140 PART | B Common Organisms and Probiotics [35.36], patients on peritoneal dialysis (A101) [37], and those with celiac disease (CECT 7347 and ES1) [38,39]. ‘Sirain BB536 improved several parameters of disease activ- ity among patients with mild-to-moderate ulcerative colitis [40] and also normalized bowel Function in elderly patients receiving enteral nutrition via a nasojejunal catheter [-11). ‘Similarly. #_longum strains have been among those thatci- {her alone or in combination otic “ameliorated symptoms in children and adults with constipa- ‘ion [42.45], Though the quality of the evidence was ad- Judged to be low, B. longum strains were also among those ‘probiotic organisms whose use lowered the prevalence of Ventilator-related pneumonia [44]. The clinical impact of B. dongum strain On impaired gut barrier function was as- sessed in a group of individuals with liver disease; though the prevalence of small intestinal bacterial overgrowth (a common occurrence in cirthosis) was reduced, no impact ‘on permeability was detected [45]. SAFETY ‘Though B. longum strains are generally regarded as safe [45.471, instances of bacteremia have been reported in pre- {erm infants [48.49] and a case of peritonitis documented {in a 42-year-old man with perforated diverticulitis (50). As ‘in many soch instances the precise impact of the probiotic strain on clinical outcome is difficult to discern. REFERENCES 1} Lae FH, O'Sulivan DI. Genomic insights into Bisdobactera, ‘Microbiol Mol Bil Rev 2010-74378-116 1B} Leahy SC, Higgins DG. Fitzgerald GF, el, Going beter wih bit obactena_J App Microbia! 2008:08:1303-15, 1B} Picard C, Flramoni J, Francois A, et al Review atic: bifsobae- texas pobitc agents physiological fects and clinical beet ‘Neat Pharmacol Ther 2005:22-495-512. (Uy Underwosd MA, Gorman JB, Lerila CB, etal. Bydobacterium longum subspecies iafants: champion enlonizes of the infant gt Pasa Res 2015:71.220-35 15} Lewis 2, Shani G, Masarwoh CF; otal. Validating bifidotacasal species and subspecios nity in commercial pebicis products Pediatr Res 2016; 7485-52. [st Seatova D, Spanova A, Spano M, etal iiciony of PCR-bat seth io csc sinning Bifotacterium longum sp longum and ‘idebateriam longa sp. fas stains of hema origin. IM robo Methods 201187106, 1 Ham 441, Loe T, Byun ML, etal Coente gonome sequence of | ‘Bitdcacteriam dongum subsp. longum KACC 1563.1 Bacteriol 20111935004, IB] Yu H, Lin Chang 7 Wang S, otal Ganome sequence of he bac- teciam Bihdobaceriom longum strain CMCC POODL, 2 probiotic sain usaf for woaing gasrimosia! dssase. Genome Anounc O11 AGOTIE-. [B] Zakharevich NV, Averoa OV. Klin KM, otal Complet ge- ome sageence of Bifidobacterium longum GIS: ideoticaion ae sharactesizaton of usique ad plobalepulatry ones. Microb Ecol 2OISToSI-M, {00} Wei ¥X, Zhang 2, Lau C, eal, Safty assessment of ifidobacte- ‘ium longum JDMBO1 based on complete genome saquances. Werld ‘J Gastrocatral 2012 18:479-88. 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Consacutve ort mlminis- ‘ton of Bidabacterian fongum MME improves the fons 55- tom agsist influnza virus ifeton by enhancing atu! Kill ell ‘activity in a murine model, Microbio!Imamnol 2015°52:1-12, “Munoz 1A, Chaoll E, Casinos B etal Now! probs Bifobacte ria longum sibs. infants CECT 7210 sein active apn ota 1s iafections. App Emvicoa Micrbiel 2011-T78775-83 An HM, Park SY, Lee DK, etal. Aobesty snd pi-lowering ef ‘ects of Bfdobacteriam pp in high fit et Anduced obese rats. Lip ie Healt Dis 2001105116, {19} Capon M, Savard P Riv A, ct al Bioaccossbl atonidants in rik fermented by Bifidobacterium langum subsp lun stains lomo Res lt 2015-2015: 69581 MacStarrJ, Maton C, Shay KH el. Inmnomadulaony ef fects of feaing with Bifidobacterium longum on ergs hung intanmaton inthe mouse Pulm Pharmacol Ther 201225:325-34, ‘You J Yagoob P Evidence of immunomulaney effet fa novel robin, ifdacteriam longa bx inftis CCUG 52586, FEMS Inmmanol Moc Microbiol 2012:65:393-42 Otyares Mf, Lapura M, Sanz Y. Oral administration of Bifdobacte- ‘ium longum CECT 7347 meats jjuml proteome ia 20 in vivo ladioindoced enteropathy animal mode. J Potsomics 2012-77 310-20. Kim JH, Jeon EJ, Hong CP, el, Exracll vscl eres potin rom Bifotaceram longum llevstes fod ary though mast call supeessin. FABoee Ca Immunol 2016: 137-307-08-1628. Schatussowa 1, Hufmgl K, Wid C. etal. Distinctive anally properties of two pobioe bacterial stabs ima mouse mad of at leg poly-seasizaton. Vacine 201|:29:1981-00, Symons EL. 'Mabooy C, Lapthor Set al. ifobacterium i {amis 39624 protets against sslnoala duced eduction in iges- ve enzyme activity in mice by stemuaton ofthe hot allmatory respooss. Cin Tras! Castrentral 2012-3215, UUndeewoed MA, Arnis J, Carer OW, tal. iobace ram logan subsp. fans experimental cocotisngenferocol aeration in inflammadon, inate immune cesponse, and the mirbiot. Pediat Res 2018765623, 1m 03) na) ns) na 07 ng) 20) en 2 Pa pg bs ba

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