Intestinal microbial-derived sphingolipids are inversely associated with childhood food allergy

[...]we adjusted for age in all analyses, performed sensitivity analyses of key results adjusting for other potential confounders, and tested for associations between mode of delivery and phenotype-associated microbiome and metabolome perturbations. [...]fecal lipid iNKT-cell activation was signific...

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Published inJournal of allergy and clinical immunology Vol. 142; no. 1; pp. 335 - 338.e9
Main Authors Lee-Sarwar, Kathleen, Kelly, Rachel S., Lasky-Su, Jessica, Moody, D. Branch, Mola, Alex R., Cheng, Tan-Yun, Comstock, Laurie E., Zeiger, Robert S., O'Connor, George T., Sandel, Megan T., Bacharier, Leonard B., Beigelman, Avraham, Laranjo, Nancy, Gold, Diane R., Bunyavanich, Supinda, Savage, Jessica H., Weiss, Scott T., Brennan, Patrick J., Litonjua, Augusto A.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.07.2018
Elsevier Limited
Subjects
Age
Antigens
Asthma
Bacteroides
Bacteroides fragilis - metabolism
Cesarean section
Child, Preschool
Children
Eigenvalues
Feces
Female
Food allergies
Food Hypersensitivity - immunology
Food Hypersensitivity - metabolism
Food Hypersensitivity - microbiology
Gastrointestinal Microbiome - immunology
Genotype & phenotype
Humans
Hypotheses
Infant
Intestine
Lipids
Male
Mediation
Metabolites
Natural Killer T-Cells - immunology
Pruritus
Sphingolipids
Sphingolipids - immunology
Sphingolipids - metabolism
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Abstract [...]we adjusted for age in all analyses, performed sensitivity analyses of key results adjusting for other potential confounders, and tested for associations between mode of delivery and phenotype-associated microbiome and metabolome perturbations. [...]fecal lipid iNKT-cell activation was significantly lower among subjects born by Cesarean section than among subjects born by vaginal delivery (P = .049). Asthma or recurrent wheeze was based on parental report of physician diagnosis of asthma or recurrent wheeze in the first 3 years of life as previously reported.4 Questionnaire responses were used to determine whether a child was ingesting breast milk and/or formula, and whether solid foods had been introduced at the time of stool sample collection as previously described.E1Fecal sample collection and profiling Stool collection and microbiome profiling methods have been described in detail previously.E2 DNA extraction was performed on the stool samples and sequencing of the bacterial 16S V3 to V5 hypervariable regions was performed by pyrosequencing (Roche 454 Titanium platform) at the Genome Center (TGI) at Washington University in St Louis, Mo. Subject Food Reaction∗ Age (mo) reported Diagnosis method Serum specific IgE (kU/L) Walnut Peanut Egg white Milk Wheat Soybean 1 Sesame seed Unknown 24 Blood and skin test <0.10 1.00 5.42 0.67 0.42 0.63 Egg Unknown 24 Other nut Unknown 24 Peanut Rash 24 2 Soy Diarrhea, nausea, hives 12 Blood and skin test <0.10 2.05 22.4 1.9 0.65 1.27 Wheat Diarrhea, nausea, hives 12 Peanut Diarrhea, nausea, hives 12 Egg Diarrhea, nausea, hives 12 Other nut Unknown 15 Fish Diarrhea, nausea, hives 24 3 Milk Hives, nausea, wheeze, worsened eczema 12 Blood test and skin test 3.05 8.72 5.03 9.88 5.06 3.89 Egg Nausea, vomiting, wheeze, sneezing/runny nose, watery eyes, hives, worsened eczema, fatigue 12 Peanut Nausea 12 Other fish Hives, nausea, diarrhea, worsened eczema, facial swelling, fussiness 12 Soy Hives, fussiness, vaginal itching, nausea, diarrhea 18 Shellfish Facial swelling, hives, worsened eczema, fussiness, nausea, diarrhea 18 Wheat Hives, fussiness, vaginal itching, nausea 21 4 Shellfish Hives, worsened eczema, nausea 12 Blood test and skin test 5.03 1.33 0.53 <0.10 0.38 0.28 Other fish Hives, worsened eczema, nausea 12 Egg Hives, wheeze, worsened eczema, nausea 12 Hot dog Hives 15 Milk Hives, worsened eczema, nausea 24 Wheat Hives 24 Peanut Hives, worsened eczema, nausea 27 5 Egg Nausea, hives, fatigue 18 Skin test 0.66 1.32 1.59 4.24 0.78 2.28 6 Peanut Hives, wheezing, sneezing, red eyes 24 History 12.7 >100 38.5 26 29 96.3 7 Other nut Eyes swelled shut, itchy 36 Skin test 0.72 2.07 4.41 8.51 1.95 0.96 8 Unknown Unknown 15 Blood test 0.25 >100 0.71 <0.10 0.15 2.2 Peanut Hives 24 9 Peanut Hives on 1 body part only 15 Blood and skin test 1.54 9.76 5.67 0.94 2.07 2.96 Egg Nausea, hives 15 Pea Hives on 1 body part only 24 Lentil Hives on 1 body part only 24 Other nut Unknown 30 10 Peanut Not asked† 12 Not asked† <0.10 0.79 0.43 0.25 0.27 <0.10 Egg Not asked† 12 11 Egg Not asked† 12 Not asked† <0.10 <0.10 0.62 <0.10 <0.10 <0.10 12 Egg Hives on 1 body part only, nausea, cough 27 Blood test <0.10 0.37 3.75 1.88 0.90 0.91 Candy/sweets Nausea 36 Table E1 Clinical history and serum specific IgE for food-allergic subjects Characteristic All children (n = 81) All subjects (n = 83) Subjects with iNKT-cell activity data (n = 57) Food allergic (n = 12) Food sensitive (n = 32) Control (n = 37) P value Food allergic (n = 8) Food sensitive (n = 22) Control (n = 27) P value Sex, n (%) .66 .17 Male 41 (51) 5 (42) 18 (56) 18 (49) 2 (25) 14 (64) 13 (48) Female 40 (49) 7 (58) 14 (44) 19 (51) 6 (75) 8 (36) 14 (52) Race/ethnicity, n (%) .94 .98 Black, non-Hispanic 34 (42) 6 (50) 13 (41) 15 (41) 4 (50) 9 (41) 10 (37) White, non-Hispanic 26 (32) 4 (33) 11 (34) 11 (30) 2 (25) 6 (27) 9 (33) Hispanic 21 (26) 2 (17) 8 (25) 11 (30) 2 (25) 7 (32) 8 (30) Birth by Cesarean section, n (%) 24 (30) 6 (50) 5 (16) 13 (35) .052 5 (63) 2 (9) 9 (33) .01 Gestational age (wk), mean ± SD 39.1 ± 1.6 39.4 ± 1.7 38.9 ± 1.9 39.4 ± 1.4 .48 39.3 ± 1.6 38.8 ± 2.2 39.4 ± 1.4 .79 Number of living children born to mother, mean ± SD 0.9 ± 0.9 1.2 ± 0.9 1.0 ± 0.9 0.8 ± 0.9 .40 1.3 ± 0.9 0.8 ± 0.8 0.8 ± 0.9 .36 Antibiotic exposure, n (%) Perinatal antibiotics 35 (43) 8 (67) 11 (34) 16 (43) .16 5 (63) 8 (36) 11 (41) .44 By age 6 mo 15 (19) 2 (17) 5 (16) 8 (22) .86 1 (13) 3 (14) 7 (26) .59 By age 3 y 69 (85) 11 (92) 29 (91) 29 (78) .36 7 (87) 21 (95) 20 (74) .10 Pet dog in home, n (%) In first 6 mo of life 22 (28) 3 (33) 6 (19) 13 (36) .31 2 (25) 3 (14) 10 (37) .19 Between age 6 and 36 mo 32 (41) 3 (33) 13 (43) 16 (43) .52 2 (25) 10 (50) 11 (41) .53 Pet cat in home, n (%) In first 6 mo of life 11 (14) 2 (17) 4 (13) 5 (14) .91 1 (13) 2 (9) 4 (15) .86 Between age 6 and 36 mo 20 (25) 6 (50) 5 (17) 9 (24) .10 3 (38) 2 (10) 6 (22) .22 Daycare by age 3 y, n (%) 43 (53) 7 (58) 15 (47) 21 (57) .72 4 (50) 10 (45) 14 (52) .93 Age at stool sample collection (mo), mean ± SD 4.6 ± 1.1 5.0 ± 1.0 5.0 ± 1.0 4.1 ± 1.0 <.01 5.0 ± 1.0 5.1 ± 1.0 4.2 ± 1.1 .02 Diet at stool sample collection, n (%) Breast-feeding 34 (42) 6 (50) 13 (41) 15 (41) .91 4 (50) 7 (32) 12 (44) .57 Formula 50 (62) 7 (58) 20 (63) 23 (62) 1 4 (50) 16 (73) 17 (63) .51 Solid foods 33 (41) 6 (50) 19 (61) 8 (22) <.01 4 (50) 12 (57) 7 (26) .07 Asthma/recurrent wheeze by age 3 y, n (%) 25 (31) 8 (67) 9 (28) 8 (22) .02 6 (75) 7 (32) 4 (15) <.01 VDAART treatment group, n (%) 1 1 4400 IU/d vitamin D 41 (51) 6 (50) 16 (50) 19 (51) 4 (50) 11 (50) 13 (48) 400 IU/d vitamin D 40 (49) 6 (50) 16 (50) 18 (49) 4 (50) 11 (50) 14 (52) Study center, n (%) .27 .71 Boston 23 (28) 4 (33) 8 (25) 11 (30) 1 (13) 2 (9) 7 (26) St Louis 42 (52) 7 (58) 20 (63) 15 (41) 3 (38) 7 (32) 9 (33) San Diego 16 (20) 1 (8) 4 (13) 11 (30) 4 (50) 13 (59) 11 (41) Maternal education, n (%) .92 .74 Less than high school 10 (12) 1 (8) 3 (9) 6 (16) 0 (0) 3 (14) 4 (15) High school or technical school 26 (32) 5 (42) 11 (34) 10 (27) 4 (50) 8 (36) 6 (22) Some college 10 (12) 2 (17) 4 (13) 4 (11) 1 (13) 3 (14) 3 (11) College graduate or graduate school 35 (43) 4 (33) 14 (44) 17 (46) 3 (38) 8 (36) 14 (52) Household income (US $), n (%) .57 .55 <30,000 29 (36) 6 (50) 12 (38) 11 (30) 5 (63) 8 (36) 8 (30) 30,000-49,999 11 (14) 1 (8) 5 (16) 5 (14) 0 (0) 4 (18) 4 (15) 50,000-74,999 9 (11) 1 (8) 3 (9) 5 (14) 1 (13) 3 (14) 4 (15) 75,000-99,999 8 (10) 1 (8) 1 (3) 6 (16) 1 (13) 0 (0) 4 (15) 100,000-149,999 10 (12) 2 (17) 2 (6) 6 (16) 1 (13) 1 (5) 4 (15) At least 150,000 5 (6) 0 (0) 4 (13) 1 (3) 0 (0) 2 (9) 1 (4) Refused to say or unknown 9 (11) 1 (8) 5 (16) 3 (8) 0 (0) 4 (18) 2 (7) Table E2 Baseline characteristics of children and upstream predictors of the intestinal microenvironment Food-allergic (n = 12) vs control (n = 37, reference) Food-sensitive (n = 32) vs control (n = 37, reference) Food-allergic (n = 12) vs food-sensitive (n = 32, reference) Metabolite Odds ratio (95% CI) P value Metabolite Odds ratio (95% CI) P value Metabolite Odds ratio (95% CI) P value 7-Methylguanine 0.29 (0.11-0.63) .004 3-Ketosphinganine 2.49 (1.37-4.89) .004 3-Hydroxypalmitate 0.23 (0.07-0.59) .01 Docosapentaenoate (n3 DPA; 22:5n3) 0.24 (0.07-0.64) .01 Pimelate (heptanedioate) 2.83 (1.38-6.29) .01 Ribonate 0.32 (0.13-0.69) .01 2-Aminophenol 3.20 (1.40-8.68) .01 Pyridoxine (vitamin B6) 3.08 (1.40-7.63) .01 1-Palmitoyl-GPI (16:0) 0.25 (0.08-0.63) .01 Bilirubin (E,Z or Z,E)∗ 0.20 (0.05-0.62) .01 Cis-urocanate 0.24 (0.07-0.66) .01 1-Palmitoyl-GPS (16:0)∗ 0.25 (0.08-0.65) .01 Histidine 0.11 (0.01-0.53) .01 Diacetylchitobiose 0.38 (0.16, -0.79) .01 I-urobilinogen 0.42 (0.20-0.79) .01 N-formylmethionine 0.28 (0.09-0.72) .01 N-acetylglutamate 0.25 (0.07-0.73) .02 Sphinganine 0.15 (0.03-0.56) .01 I-urobilinogen 0.43 (0.20-0.82) .02 5alpha-pregnan-3beta,20alpha-diol monosulfate (1) 3.04 (1.31-8.77) .02 2-Methylserine 0.32 (0.11-0.75) .02 Dihomo-linolenate (20:3n3 or n6) 0.25 (0.06-0.66) .02 N-carbamoylaspartate 0.38 (0.15-0.81) .02 13-Methylmyristate 0.39 (0.17-0.82) .02 Serine 0.11 (0.01-0.59) .02 N-acetylasparagine 0.26 (0.08-0.78) .02 Dihomo-linolenate (20:3n3 or n6) 0.24 (0.06-0.67) .02 2-Methylserine 0.20 (0.04-0.68) .03 Lysylleucine 2.23 (1.15-4.69) .02 Glycylisoleucine 0.25 (0.07-0.70) .02 5,6-Dihydrothymine 0.40 (0.16-0.86) .03 Vanillic alcohol sulfate 0.42 (0.18-0.86) .03 D-urobilin 0.40 (0.17-0.83) .02 3-Hydroxypalmitate 0.27 (0.07-0.79) .03 Docosahexenoylcarnitine (C22:6)∗ 0.37 (0.14-0.83) .03 Docosapentaenoate (n3 DPA; 22:5n3) 0.26 (0.07-0.74) .02 Phenethylamine 0.32 (0.10-0.83) .03 Ursodeoxycholate sulfate (1) 0.57 (0.34-0.92) .03 7-Methylguanine 0.47 (0.23-0.90) .03 D-urobilin 0.42 (0.18-0.91) .04 3-Methylglutarate/2-methylglutarate 2.35 (1.14-5.35) .03 Sucrose 0.37 (0.14-0.85) .03 Ursodeoxycholate sulfate (1) 0.45 (0.20-0.90) .04 N-palmitoylserine 1.87 (1.08-3.36) .03 1-Palmitoyl-GPE (16:0) 0.20 (0.04-0.73) .03 Tryptamine 0.44 (0.19-0.90) .04 Malonylcarnitine 0.39 (0.16-0.87) .03 21-Hydroxypregnenolone disulfate 0.31 (0.09-0.80) .03 2,3-Dimethylsuccinate 3.06 (1.09-9.72) .04 13-Methylmyristate 1.97 (1.08-3.80) .03 N-acetylglycine 3.33 (1.21-11.18) .03 Oleoyl-linoleoyl-glycerol (18:1/18:2) [1] 2.56 (1.09-6.94) .04 Dopamine 3-O-sulfate 0.45 (0.21-0.90) .03 Alpha-CEHC 0.32 (0.10-0.840) .03 Palmitoyl-linoleoyl-glycerol (16:0/18:2) [1]∗ 2.56 (1.08-7.07) .04 Glutaminylleucine 2.58 (1.12-6.57) .03 Glycerophosphoserine∗ 0.28 (0.08-0.82) .03 Tyrosine 0.16 (0.02-0.86) .04 N2,N6-diacetyllysine 0.41 (0.17-0.90) .03 Bilirubin (E,Z or Z,E)∗ 0.32 (0.10-0.87) .04 Formiminoglutamate 0.36 (0.11-0.90) .04 N-acetyl-aspartyl-glutamate (NAAG) 0.41 (0.17-0.91) .04 Glycylvaline 0.24 (0.05-0.87) .04 Linolenate (alpha or gamma; [18:3n3 or 6]) 0.27 (0.06-0.86) .04 N-alpha-acetylornithine 0.39 (0.15-0.91) .04 Linoleoyl ethanolamide 0.42 (0.17-0.94) .04 Linoleoyl-linolenoyl-glycerol (18:2/18:3) [2]∗ 2.39 (1.04-6.06) .05 Allo-threonine 0.40 (0.15-0.90) .04 3-Ureidoisobutyrate 0.45 (
AbstractList [...]we adjusted for age in all analyses, performed sensitivity analyses of key results adjusting for other potential confounders, and tested for associations between mode of delivery and phenotype-associated microbiome and metabolome perturbations. [...]fecal lipid iNKT-cell activation was significantly lower among subjects born by Cesarean section than among subjects born by vaginal delivery (P = .049). Asthma or recurrent wheeze was based on parental report of physician diagnosis of asthma or recurrent wheeze in the first 3 years of life as previously reported.4 Questionnaire responses were used to determine whether a child was ingesting breast milk and/or formula, and whether solid foods had been introduced at the time of stool sample collection as previously described.E1Fecal sample collection and profiling Stool collection and microbiome profiling methods have been described in detail previously.E2 DNA extraction was performed on the stool samples and sequencing of the bacterial 16S V3 to V5 hypervariable regions was performed by pyrosequencing (Roche 454 Titanium platform) at the Genome Center (TGI) at Washington University in St Louis, Mo. Subject Food Reaction∗ Age (mo) reported Diagnosis method Serum specific IgE (kU/L) Walnut Peanut Egg white Milk Wheat Soybean 1 Sesame seed Unknown 24 Blood and skin test <0.10 1.00 5.42 0.67 0.42 0.63 Egg Unknown 24 Other nut Unknown 24 Peanut Rash 24 2 Soy Diarrhea, nausea, hives 12 Blood and skin test <0.10 2.05 22.4 1.9 0.65 1.27 Wheat Diarrhea, nausea, hives 12 Peanut Diarrhea, nausea, hives 12 Egg Diarrhea, nausea, hives 12 Other nut Unknown 15 Fish Diarrhea, nausea, hives 24 3 Milk Hives, nausea, wheeze, worsened eczema 12 Blood test and skin test 3.05 8.72 5.03 9.88 5.06 3.89 Egg Nausea, vomiting, wheeze, sneezing/runny nose, watery eyes, hives, worsened eczema, fatigue 12 Peanut Nausea 12 Other fish Hives, nausea, diarrhea, worsened eczema, facial swelling, fussiness 12 Soy Hives, fussiness, vaginal itching, nausea, diarrhea 18 Shellfish Facial swelling, hives, worsened eczema, fussiness, nausea, diarrhea 18 Wheat Hives, fussiness, vaginal itching, nausea 21 4 Shellfish Hives, worsened eczema, nausea 12 Blood test and skin test 5.03 1.33 0.53 <0.10 0.38 0.28 Other fish Hives, worsened eczema, nausea 12 Egg Hives, wheeze, worsened eczema, nausea 12 Hot dog Hives 15 Milk Hives, worsened eczema, nausea 24 Wheat Hives 24 Peanut Hives, worsened eczema, nausea 27 5 Egg Nausea, hives, fatigue 18 Skin test 0.66 1.32 1.59 4.24 0.78 2.28 6 Peanut Hives, wheezing, sneezing, red eyes 24 History 12.7 >100 38.5 26 29 96.3 7 Other nut Eyes swelled shut, itchy 36 Skin test 0.72 2.07 4.41 8.51 1.95 0.96 8 Unknown Unknown 15 Blood test 0.25 >100 0.71 <0.10 0.15 2.2 Peanut Hives 24 9 Peanut Hives on 1 body part only 15 Blood and skin test 1.54 9.76 5.67 0.94 2.07 2.96 Egg Nausea, hives 15 Pea Hives on 1 body part only 24 Lentil Hives on 1 body part only 24 Other nut Unknown 30 10 Peanut Not asked† 12 Not asked† <0.10 0.79 0.43 0.25 0.27 <0.10 Egg Not asked† 12 11 Egg Not asked† 12 Not asked† <0.10 <0.10 0.62 <0.10 <0.10 <0.10 12 Egg Hives on 1 body part only, nausea, cough 27 Blood test <0.10 0.37 3.75 1.88 0.90 0.91 Candy/sweets Nausea 36 Table E1 Clinical history and serum specific IgE for food-allergic subjects Characteristic All children (n = 81) All subjects (n = 83) Subjects with iNKT-cell activity data (n = 57) Food allergic (n = 12) Food sensitive (n = 32) Control (n = 37) P value Food allergic (n = 8) Food sensitive (n = 22) Control (n = 27) P value Sex, n (%) .66 .17 Male 41 (51) 5 (42) 18 (56) 18 (49) 2 (25) 14 (64) 13 (48) Female 40 (49) 7 (58) 14 (44) 19 (51) 6 (75) 8 (36) 14 (52) Race/ethnicity, n (%) .94 .98 Black, non-Hispanic 34 (42) 6 (50) 13 (41) 15 (41) 4 (50) 9 (41) 10 (37) White, non-Hispanic 26 (32) 4 (33) 11 (34) 11 (30) 2 (25) 6 (27) 9 (33) Hispanic 21 (26) 2 (17) 8 (25) 11 (30) 2 (25) 7 (32) 8 (30) Birth by Cesarean section, n (%) 24 (30) 6 (50) 5 (16) 13 (35) .052 5 (63) 2 (9) 9 (33) .01 Gestational age (wk), mean ± SD 39.1 ± 1.6 39.4 ± 1.7 38.9 ± 1.9 39.4 ± 1.4 .48 39.3 ± 1.6 38.8 ± 2.2 39.4 ± 1.4 .79 Number of living children born to mother, mean ± SD 0.9 ± 0.9 1.2 ± 0.9 1.0 ± 0.9 0.8 ± 0.9 .40 1.3 ± 0.9 0.8 ± 0.8 0.8 ± 0.9 .36 Antibiotic exposure, n (%) Perinatal antibiotics 35 (43) 8 (67) 11 (34) 16 (43) .16 5 (63) 8 (36) 11 (41) .44 By age 6 mo 15 (19) 2 (17) 5 (16) 8 (22) .86 1 (13) 3 (14) 7 (26) .59 By age 3 y 69 (85) 11 (92) 29 (91) 29 (78) .36 7 (87) 21 (95) 20 (74) .10 Pet dog in home, n (%) In first 6 mo of life 22 (28) 3 (33) 6 (19) 13 (36) .31 2 (25) 3 (14) 10 (37) .19 Between age 6 and 36 mo 32 (41) 3 (33) 13 (43) 16 (43) .52 2 (25) 10 (50) 11 (41) .53 Pet cat in home, n (%) In first 6 mo of life 11 (14) 2 (17) 4 (13) 5 (14) .91 1 (13) 2 (9) 4 (15) .86 Between age 6 and 36 mo 20 (25) 6 (50) 5 (17) 9 (24) .10 3 (38) 2 (10) 6 (22) .22 Daycare by age 3 y, n (%) 43 (53) 7 (58) 15 (47) 21 (57) .72 4 (50) 10 (45) 14 (52) .93 Age at stool sample collection (mo), mean ± SD 4.6 ± 1.1 5.0 ± 1.0 5.0 ± 1.0 4.1 ± 1.0 <.01 5.0 ± 1.0 5.1 ± 1.0 4.2 ± 1.1 .02 Diet at stool sample collection, n (%) Breast-feeding 34 (42) 6 (50) 13 (41) 15 (41) .91 4 (50) 7 (32) 12 (44) .57 Formula 50 (62) 7 (58) 20 (63) 23 (62) 1 4 (50) 16 (73) 17 (63) .51 Solid foods 33 (41) 6 (50) 19 (61) 8 (22) <.01 4 (50) 12 (57) 7 (26) .07 Asthma/recurrent wheeze by age 3 y, n (%) 25 (31) 8 (67) 9 (28) 8 (22) .02 6 (75) 7 (32) 4 (15) <.01 VDAART treatment group, n (%) 1 1 4400 IU/d vitamin D 41 (51) 6 (50) 16 (50) 19 (51) 4 (50) 11 (50) 13 (48) 400 IU/d vitamin D 40 (49) 6 (50) 16 (50) 18 (49) 4 (50) 11 (50) 14 (52) Study center, n (%) .27 .71 Boston 23 (28) 4 (33) 8 (25) 11 (30) 1 (13) 2 (9) 7 (26) St Louis 42 (52) 7 (58) 20 (63) 15 (41) 3 (38) 7 (32) 9 (33) San Diego 16 (20) 1 (8) 4 (13) 11 (30) 4 (50) 13 (59) 11 (41) Maternal education, n (%) .92 .74 Less than high school 10 (12) 1 (8) 3 (9) 6 (16) 0 (0) 3 (14) 4 (15) High school or technical school 26 (32) 5 (42) 11 (34) 10 (27) 4 (50) 8 (36) 6 (22) Some college 10 (12) 2 (17) 4 (13) 4 (11) 1 (13) 3 (14) 3 (11) College graduate or graduate school 35 (43) 4 (33) 14 (44) 17 (46) 3 (38) 8 (36) 14 (52) Household income (US $), n (%) .57 .55 <30,000 29 (36) 6 (50) 12 (38) 11 (30) 5 (63) 8 (36) 8 (30) 30,000-49,999 11 (14) 1 (8) 5 (16) 5 (14) 0 (0) 4 (18) 4 (15) 50,000-74,999 9 (11) 1 (8) 3 (9) 5 (14) 1 (13) 3 (14) 4 (15) 75,000-99,999 8 (10) 1 (8) 1 (3) 6 (16) 1 (13) 0 (0) 4 (15) 100,000-149,999 10 (12) 2 (17) 2 (6) 6 (16) 1 (13) 1 (5) 4 (15) At least 150,000 5 (6) 0 (0) 4 (13) 1 (3) 0 (0) 2 (9) 1 (4) Refused to say or unknown 9 (11) 1 (8) 5 (16) 3 (8) 0 (0) 4 (18) 2 (7) Table E2 Baseline characteristics of children and upstream predictors of the intestinal microenvironment Food-allergic (n = 12) vs control (n = 37, reference) Food-sensitive (n = 32) vs control (n = 37, reference) Food-allergic (n = 12) vs food-sensitive (n = 32, reference) Metabolite Odds ratio (95% CI) P value Metabolite Odds ratio (95% CI) P value Metabolite Odds ratio (95% CI) P value 7-Methylguanine 0.29 (0.11-0.63) .004 3-Ketosphinganine 2.49 (1.37-4.89) .004 3-Hydroxypalmitate 0.23 (0.07-0.59) .01 Docosapentaenoate (n3 DPA; 22:5n3) 0.24 (0.07-0.64) .01 Pimelate (heptanedioate) 2.83 (1.38-6.29) .01 Ribonate 0.32 (0.13-0.69) .01 2-Aminophenol 3.20 (1.40-8.68) .01 Pyridoxine (vitamin B6) 3.08 (1.40-7.63) .01 1-Palmitoyl-GPI (16:0) 0.25 (0.08-0.63) .01 Bilirubin (E,Z or Z,E)∗ 0.20 (0.05-0.62) .01 Cis-urocanate 0.24 (0.07-0.66) .01 1-Palmitoyl-GPS (16:0)∗ 0.25 (0.08-0.65) .01 Histidine 0.11 (0.01-0.53) .01 Diacetylchitobiose 0.38 (0.16, -0.79) .01 I-urobilinogen 0.42 (0.20-0.79) .01 N-formylmethionine 0.28 (0.09-0.72) .01 N-acetylglutamate 0.25 (0.07-0.73) .02 Sphinganine 0.15 (0.03-0.56) .01 I-urobilinogen 0.43 (0.20-0.82) .02 5alpha-pregnan-3beta,20alpha-diol monosulfate (1) 3.04 (1.31-8.77) .02 2-Methylserine 0.32 (0.11-0.75) .02 Dihomo-linolenate (20:3n3 or n6) 0.25 (0.06-0.66) .02 N-carbamoylaspartate 0.38 (0.15-0.81) .02 13-Methylmyristate 0.39 (0.17-0.82) .02 Serine 0.11 (0.01-0.59) .02 N-acetylasparagine 0.26 (0.08-0.78) .02 Dihomo-linolenate (20:3n3 or n6) 0.24 (0.06-0.67) .02 2-Methylserine 0.20 (0.04-0.68) .03 Lysylleucine 2.23 (1.15-4.69) .02 Glycylisoleucine 0.25 (0.07-0.70) .02 5,6-Dihydrothymine 0.40 (0.16-0.86) .03 Vanillic alcohol sulfate 0.42 (0.18-0.86) .03 D-urobilin 0.40 (0.17-0.83) .02 3-Hydroxypalmitate 0.27 (0.07-0.79) .03 Docosahexenoylcarnitine (C22:6)∗ 0.37 (0.14-0.83) .03 Docosapentaenoate (n3 DPA; 22:5n3) 0.26 (0.07-0.74) .02 Phenethylamine 0.32 (0.10-0.83) .03 Ursodeoxycholate sulfate (1) 0.57 (0.34-0.92) .03 7-Methylguanine 0.47 (0.23-0.90) .03 D-urobilin 0.42 (0.18-0.91) .04 3-Methylglutarate/2-methylglutarate 2.35 (1.14-5.35) .03 Sucrose 0.37 (0.14-0.85) .03 Ursodeoxycholate sulfate (1) 0.45 (0.20-0.90) .04 N-palmitoylserine 1.87 (1.08-3.36) .03 1-Palmitoyl-GPE (16:0) 0.20 (0.04-0.73) .03 Tryptamine 0.44 (0.19-0.90) .04 Malonylcarnitine 0.39 (0.16-0.87) .03 21-Hydroxypregnenolone disulfate 0.31 (0.09-0.80) .03 2,3-Dimethylsuccinate 3.06 (1.09-9.72) .04 13-Methylmyristate 1.97 (1.08-3.80) .03 N-acetylglycine 3.33 (1.21-11.18) .03 Oleoyl-linoleoyl-glycerol (18:1/18:2) [1] 2.56 (1.09-6.94) .04 Dopamine 3-O-sulfate 0.45 (0.21-0.90) .03 Alpha-CEHC 0.32 (0.10-0.840) .03 Palmitoyl-linoleoyl-glycerol (16:0/18:2) [1]∗ 2.56 (1.08-7.07) .04 Glutaminylleucine 2.58 (1.12-6.57) .03 Glycerophosphoserine∗ 0.28 (0.08-0.82) .03 Tyrosine 0.16 (0.02-0.86) .04 N2,N6-diacetyllysine 0.41 (0.17-0.90) .03 Bilirubin (E,Z or Z,E)∗ 0.32 (0.10-0.87) .04 Formiminoglutamate 0.36 (0.11-0.90) .04 N-acetyl-aspartyl-glutamate (NAAG) 0.41 (0.17-0.91) .04 Glycylvaline 0.24 (0.05-0.87) .04 Linolenate (alpha or gamma; [18:3n3 or 6]) 0.27 (0.06-0.86) .04 N-alpha-acetylornithine 0.39 (0.15-0.91) .04 Linoleoyl ethanolamide 0.42 (0.17-0.94) .04 Linoleoyl-linolenoyl-glycerol (18:2/18:3) [2]∗ 2.39 (1.04-6.06) .05 Allo-threonine 0.40 (0.15-0.90) .04 3-Ureidoisobutyrate 0.45 (
Author Zeiger, Robert S.
Beigelman, Avraham
Laranjo, Nancy
O'Connor, George T.
Lee-Sarwar, Kathleen
Brennan, Patrick J.
Moody, D. Branch
Bunyavanich, Supinda
Bacharier, Leonard B.
Kelly, Rachel S.
Cheng, Tan-Yun
Gold, Diane R.
Savage, Jessica H.
Weiss, Scott T.
Sandel, Megan T.
Lasky-Su, Jessica
Litonjua, Augusto A.
Mola, Alex R.
Comstock, Laurie E.
AuthorAffiliation a Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass
c Division of Infectious Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass
e Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Mass
h Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Mass
i Department of Pediatrics – Allergy/Immunology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
d Kaiser Permanente Southern California, San Diego, Calif
g Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine and St Louis Children’s Hospital, St Louis, Mo
b Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass
f Department of Pediatrics, Boston Medical Center, Boston, Mass
AuthorAffiliation_xml – name: h Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Mass
– name: g Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine and St Louis Children’s Hospital, St Louis, Mo
– name: i Department of Pediatrics – Allergy/Immunology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
– name: f Department of Pediatrics, Boston Medical Center, Boston, Mass
– name: b Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass
– name: a Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass
– name: e Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Mass
– name: d Kaiser Permanente Southern California, San Diego, Calif
– name: c Division of Infectious Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass
Author_xml – sequence: 1
  givenname: Kathleen
  surname: Lee-Sarwar
  fullname: Lee-Sarwar, Kathleen
  email: klee-sarwar@partners.org
  organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 2
  givenname: Rachel S.
  surname: Kelly
  fullname: Kelly, Rachel S.
  organization: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
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  givenname: Jessica
  surname: Lasky-Su
  fullname: Lasky-Su, Jessica
  organization: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 4
  givenname: D. Branch
  surname: Moody
  fullname: Moody, D. Branch
  organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 5
  givenname: Alex R.
  surname: Mola
  fullname: Mola, Alex R.
  organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 6
  givenname: Tan-Yun
  surname: Cheng
  fullname: Cheng, Tan-Yun
  organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 7
  givenname: Laurie E.
  surname: Comstock
  fullname: Comstock, Laurie E.
  organization: Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 8
  givenname: Robert S.
  surname: Zeiger
  fullname: Zeiger, Robert S.
  organization: Kaiser Permanente Southern California, San Diego, Calif
– sequence: 9
  givenname: George T.
  surname: O'Connor
  fullname: O'Connor, George T.
  organization: Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Mass
– sequence: 10
  givenname: Megan T.
  surname: Sandel
  fullname: Sandel, Megan T.
  organization: Department of Pediatrics, Boston Medical Center, Boston, Mass
– sequence: 11
  givenname: Leonard B.
  surname: Bacharier
  fullname: Bacharier, Leonard B.
  organization: Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo
– sequence: 12
  givenname: Avraham
  surname: Beigelman
  fullname: Beigelman, Avraham
  organization: Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo
– sequence: 13
  givenname: Nancy
  surname: Laranjo
  fullname: Laranjo, Nancy
  organization: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 14
  givenname: Diane R.
  surname: Gold
  fullname: Gold, Diane R.
  organization: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 15
  givenname: Supinda
  surname: Bunyavanich
  fullname: Bunyavanich, Supinda
  organization: Department of Pediatrics – Allergy/Immunology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
– sequence: 16
  givenname: Jessica H.
  surname: Savage
  fullname: Savage, Jessica H.
  organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 17
  givenname: Scott T.
  surname: Weiss
  fullname: Weiss, Scott T.
  organization: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 18
  givenname: Patrick J.
  surname: Brennan
  fullname: Brennan, Patrick J.
  organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
– sequence: 19
  givenname: Augusto A.
  surname: Litonjua
  fullname: Litonjua, Augusto A.
  email: augusto_litonjua@urmc.rochester.edu
  organization: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29729303$$D View this record in MEDLINE/PubMed
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These authors contributed equally to this work.
Current/present address: Jessica H. Savage is currently at Vertex Pharmaceuticals, Boston, Mass and Augusto A. Litonjua is at the Division of Pediatric Pulmonary Medicine, Golisano Children’s Hospital at University of Rochester Medical Center, Rochester, NY.
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PublicationTitle Journal of allergy and clinical immunology
PublicationTitleAlternate J Allergy Clin Immunol
PublicationYear 2018
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Elsevier Limited
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Snippet [...]we adjusted for age in all analyses, performed sensitivity analyses of key results adjusting for other potential confounders, and tested for associations...
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SubjectTerms Age
Antigens
Asthma
Bacteroides
Bacteroides fragilis - metabolism
Cesarean section
Child, Preschool
Children
Eigenvalues
Feces
Female
Food allergies
Food Hypersensitivity - immunology
Food Hypersensitivity - metabolism
Food Hypersensitivity - microbiology
Gastrointestinal Microbiome - immunology
Genotype & phenotype
Humans
Hypotheses
Infant
Intestine
Lipids
Male
Mediation
Metabolites
Natural Killer T-Cells - immunology
Pruritus
Sphingolipids
Sphingolipids - immunology
Sphingolipids - metabolism
Title Intestinal microbial-derived sphingolipids are inversely associated with childhood food allergy
URI https://www.clinicalkey.com/#!/content/1-s2.0-S0091674918306286
https://dx.doi.org/10.1016/j.jaci.2018.04.016
https://www.ncbi.nlm.nih.gov/pubmed/29729303
https://www.proquest.com/docview/2063221213
https://www.proquest.com/docview/2035247813
https://pubmed.ncbi.nlm.nih.gov/PMC6433125
Volume 142
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