Secretor Research Articles

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.

Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.

Interactions between human milk oligosaccharides, microbiota and immune factors in milk of women with and without mastitis

Lactational mastitis is an excellent target to study possible interactions between HMOs, immune factors and milk microbiota due to the infectious and inflammatory nature of this condition. In this work, microbiological, immunological and HMO profiles of milk samples from women with (MW) or without (HW) mastitis were compared. Secretor status in women (based on HMO profile) was not associated to mastitis. DFLNH, LNFP II and LSTb concentrations in milk were higher in samples from HW than from MW among Secretor women. Milk from HW was characterized by a low bacterial load (dominated by Staphylococcus epidermidis and streptococci), high prevalence of IL10 and IL13, and low sialylated HMO concentration. In contrast, high levels of staphylococci, streptococci, IFNγ and IL12 characterized milk from MW. A comparison between subacute (SAM) and acute (AM) mastitis cases revealed differences related to the etiological agent (S. epidermidis in SAM; Staphylococcus aureus in AM), milk immunological profile (high content of IL10 and IL13 in SAM and IL2 in AM) and milk HMOs profile (high content of 3FL in SAM and of LNT, LNnT, and LSTc in AM). These results suggest that microbiological, immunological and HMOs profiles of milk are related to mammary health of women.

Interaction of dental anxiety and ABO secretor status of blood group on dental caries in a group of children

Objective: To evaluate the interaction of the dental anxiety precedents at the first dental examination andthe AB secretor status of blood groups (A, B, AB, and O) on dental caries experience and severity in a groupof school children. Material and Methods: This is a cross-sectional study included 81 healthy children aged6-8 years from primary schools in Baghdad; with negative previous dental visit. Dental anxiety represented byphysiological measures was measured by pulse oximeter. Dental caries experience and severity was recorded.Unstimulated salivary samples were taken from the children to determine the salivary secretor status for ABblood type. Results: The anxiety was decreased as age increases; boys were more anxious than girls; and moreanxious children were found in non-secretor group; Dental caries was higher in non-secretor anxious childrenall with non-significant difference. Conclusion: There is little evidence that the AB secretor status and anxietyto have influence on dental caries experience and severity, as there are many factors may interact to propagatethe caries experience and severity.KEYWORDSDental anxiety; Dental caries; Children.

A Cross-Sectional Assessment of Human Milk Oligosaccharide Composition of Vegan, Vegetarian, and Nonvegetarian Mothers.

Purpose: Recently, maternal nutrient intake has been associated with human milk oligosaccharides (HMOs) composition. The goal of this study was to assess HMO composition in breast milk samples from vegan, vegetarian, and nonvegetarian lactating women. Second, we assessed impact of maternal body mass index (BMI), age, parity, and lactation stage on HMO composition. Materials and Methods: A cross-sectional analysis of HMO composition from vegan (n = 26), vegetarian (n = 22), and nonvegetarian (n = 26) lactating women was carried out. The majority of participants took dietary supplements. Results: In an unadjusted bivariate model, there was no difference in individual HMO composition, total HMO-bound fucose and HMO-bound sialic acid, or diversity and evenness scores by diet group. When adjusting for factors that significantly differed between groups (maternal BMI and lactation stage), no differences in HMO composition were observed. Secretor status was significant for 13 of the outcome variables with the strongest positive relationship with total HMO (β = 0.922) and HMO-bound fucose (β = 0.910), and the strongest negative relationship with sialyl-lacto-N-tetraose b (LSTb) (β = -0.544). Lactation stage was significant for eight analytes, with the strongest positive impact on 3'sialyllactose (3'SL) (β = 0.433), and the strongest negative impact on 6'sialyllactose (6'SL) (β = -0.519). Maternal BMI had a significant positive relationship with total HMO composition (β = 0.113) and 3'SL (β = 0.325). Conclusions: Lactating women who consume plant-based diets do not produce different breast milk as it relates to HMO composition.

The Human-Milk Oligosaccharide Profile of Lactating Women in Dhaka, Bangladesh.

ABSTRACTBackgroundHuman-milk oligosaccharides (HMOs) are an abundant component of human milk that have health-related effects on breastfeeding infants. Since variation in HMO composition can be explained by maternal and environmental factors, understanding the diversity in HMOs across settings and identifying context-specific factors associated with HMO abundances is important.ObjectivesThe aim was to describe the HMO profile of Bangladeshi women and to estimate the effect of maternal vitamin D supplementation on HMO composition.MethodsIn a cross-sectional analysis of data and samples from the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh (clinicaltrials.gov; NCT01924013), 192 participants were randomly selected including 96 from each of the placebo and highest-dose vitamin D supplementation groups. In mid-feed breast milk samples collected at a mean (±SD) postpartum age of 93 ± 7 d, absolute and relative abundances of 19 HMOs were analyzed by HPLC. “Secretors” were defined as participants with 2′fucosyllactose concentrations >350 nmol/mL. Associations between HMO concentrations and selected maternal or environmental factors were estimated by multivariable linear regression, adjusting for vitamin D group allocation and secretor status. HMO profiles of Bangladeshi women were compared with data from other international cohorts.ResultsOverall, 34% (65/192) of participants were nonsecretors. Secretor status was associated with the concentrations of total HMOs and 79% (15/19) of individual HMOs. Vitamin D supplementation did not affect the total or individual concentration of any measured HMO. 3-Fucosyllactose concentration was significantly higher in breast milk samples collected in December to February compared with samples collected in March to May. HMO composition was similar to other previously reported cohorts.ConclusionsThe HMO profile of Bangladeshi women is predominantly determined by secretor status. Context-specific HMO data may improve understanding of the effects of HMOs on the infant microbiome and health and guide the development of HMO-containing interventions.

Fecal Microbiota Transplantation As a Therapeutic Option for Graft-Versus-Host-Disease: A Systematic Review and Future Directions

Introduction:In recent years, there has been an expanding focus on interplay between intestinal microbiotal diversity and outcome of acute graft versus host disease(GVHD) in hematopoietic stem cell transplantation (HCT) recipients. One of the compelling intervention to maintain healthy gut microbiota for better outcome of GVHD in HCT recipients is Fecal microbial transplantation(FMT). Several non randomized small clinical studies and case reports on the efficacy and safety of FMT were reported so far. However, the ultimate role of FMT as a therapeutic option to treat GVHD is yet to be determined due to lack of randomised, large scale, statistically significant studies. Here in, we report a systemic review of literature available so far in an effort to establish a definite role of FMT.Methodology: A systemic literature search was conducted using various electronic databases. The case reports, case series and clinical studies related to FMT were used as a therapeutic or preventative modality specifically for GVHD are included.Results: Upon pooling of data, 87 patients from 6 studies and 5 case reports were included in the study in which complete remission(CR) occured in 43.7% and partial remission(PR) occured in 20.7% patients which is equivalent to 64.4% overall response rate in treating GVHD. Furthermore, out of all the species in fecal matter, clostridium was found to be the most valuable species in decreasing the rates of GVHD re-occurrence. Only a limited number of patients had treatment-related mortality(TRM) from GVHD while few showed mild GI-related (abdominal pain/distention, nausea, regurgitation) and non-GI adverse reactions including infections, anemia, thrombocytopenia, paroxysmal, and atrial fibrillation. We emphasize that the most of the patients did not have any major complications after FMT.Conclusion:We conclude that the FMT is a safe and effective strategy for the management of GVHD based on our study. The establishment of gut diversity along with the patient's intrinsic factors like fucosyltransferase 2 (FUT2) secretor status and baseline gut microbial diversity play a major role in the success of FMT. Given the restricted size and absence of randomized data, one cannot portray FMT as a standard of care yet, however, the low or absent toxicity along with improvement in survival justifies this modality to be tested in a randomized fashion. We strongly encourage the transplant community to enroll patients in innovative trials utilizing FMT, as this may be a one of the safest strategies for both prevention and treatment of GVHD DisclosuresNo relevant conflicts of interest to declare.

Point-of-care human milk testing for maternal secretor status

We present an electrochemical impedimetric-based biosensor for monitoring the variation in human milk oligosaccharide (HMO) composition. 2′-Fucosyllactose (2’FL) is an HMO associated with infant growth, cognitive development, and protection from infectious diarrhea, one of the major causes of infant death worldwide. Due to genetic variation, the milk of some women (non-secretors) contains no or very little 2′FL with potential implications for infant health and development. However, there is currently no technology to analyze the presence and concentration of HMOs in human milk at the point-of-care (POC). The lack of such technology represents a major impediment to advancing human milk research and improving maternal-infant health. Towards this unmet need, we report an impedimetric assay for HMOs with an α-1,2 linkage, the most abundant of which is 2′FL. The sensor uses a lectin for affinity, specifically Ulex europaeusagglutininI (UEA), with electrochemical readout. In spiked studies, the sensor exhibited a high degree of linearity (R2 = 0.991) over 0.5 to 3.0 μM with a 330-nM detection limit. The sensor performance was clinically validated using banked human milk samples and correctly identified all secretor vs. non-secretor samples. Furthermore, despite the short 35-min assay time and low sample volume (25 μL), the assay was highly correlated with HPLC measurements. This bedside human milk testing assay enables POC, “sample-to-answer” quantitative HMO measurement, and will be a valuable tool to assess milk composition.Graphical abstract

Oligosaccharides and Microbiota in Human Milk Are Interrelated at 3 Months Postpartum in a Cohort of Women with a High Prevalence of Gestational Impaired Glucose Tolerance

BackgroundHuman milk is a rich source of human milk oligosaccharides (HMOs) and bacteria. It is unclear how these components interact within the breast microenvironment. ObjectivesThe objectives were first, to investigate the association between maternal characteristics and HMOs, and second, to assess the association between HMOs and microbial community composition and predicted function in milk from women with high rates of gestational glucose intolerance. MethodsThis was an exploratory analysis of a previously completed prospective cohort study (NCT01405547) where milk samples (n = 107) were collected at 3 mo postpartum. Milk microbiota composition was analyzed by V4-16S ribosomal RNA gene sequencing and HMOs by rapid high-throughput HPLC. Data were stratified and analyzed by maternal secretor status phenotype and associations between HMOs and microbiota were determined using linear regression models (ɑ-diversity), Adonis (B-diversity), Poisson regression models (differential abundance), and general linear models (predicted microbial function). ResultsPrepregnancy BMI, race, and frequency of direct breastfeeding, but not gestational glucose intolerance, were found to be significantly associated with a number of HMOs among secretors and non-secretors. Fucosyllacto-N-hexaose was negatively associated with microbial richness (Chao1) among secretors [B-estimate (SE): −9.3 × 102 (3.4 × 102); P= 0.0082] and difucosyllacto-N-hexaose was negatively associated with microbiota diversity (Shannon index) [−1.7 (0.78); P= 0.029] among secretors. Lacto-N-neotetraose (LNnT) was associated with both microbial B-diversity (weighted UniFrac R2= 0.040, P= 0.036) and KEGG ortholog B-diversity (Bray-Curtis R2= 0.039, P= 0.043) in secretors. Additionally, difucosyllactose in secretors and disialyllacto-N-hexaose and LNnT in non-secretors were associated with enrichment of predicted microbial genes encoding for metabolism- and infection-related pathways (P-false discovery rate < 0.1). ConclusionsHMOs are associated with the microbial composition and predicted microbial functions in human milk at 3 mo postpartum. Further research is needed to investigate the role these relations play in maternal and infant health.

Concentrations of oligosaccharides in human milk and child growth

BackgroundThe relationship between human milk oligosaccharides (HMO) and child growth has been investigated only insufficiently with ambiguous results. Therefore, this study examines potential influencing factors of HMO concentrations and how HMO are associated with child growth parameters.MethodsMilk samples from the German LIFE Child cohort of healthy children were analyzed for 9 HMO. Putative associations with maternal and child cofactors and child height, head circumference and BMI between 3 months and 7 years of age were examined. Secretor status, defined as the presence of 2′-fucosyllactose, was investigated for associations with infant outcomes.ResultsOur population consisted of 21 (14.7%) non-secretor and 122 (85.3%) secretor mothers. Maternal age was significantly associated with higher 3′SL concentrations; gestational age was associated with LNT, 6′SL and LNFP-I. Pre-pregnancy BMI was negatively associated with LNnT only in non-secretors. The growth velocity of non-secretors’ children was inversely associated with LNnT at 3 months to 1 year (R = 0.95 [0.90, 0.99], p = 0.014), 1 to 2 years (R = 0.80 [0.72, 0.88], p < 0.001) and 5 to 6 years (R = 0.71 [0.57, 0.87], p = 0.002). 2’FL was negatively associated with BMI consistently, reaching statistical significance at 3 months and 4 and 5 years. Children of non-secretors showed higher BMI at 3 months, 6 months, and 3, 6, and 7 years of age.ConclusionWe found that some associations between HMO and infant growth may extend beyond the infancy and breastfeeding periods. They highlight the importance of both maternal and infant parameters in the understanding of the underlying associations.Trial registrationThe study is registered with ClinicalTrial.gov: NCT02550236.

Histo-Blood Group Antigens, Enteropathogen Carriage and Environmental Enteropathy in Stunted Zambian Children.

Stunting, the most common form of childhood undernutrition, is associated with environmental enteropathy (EE). Enteric infections are believed to play a role in the pathophysiology of EE and stunting though the exact mechanism remains undetermined. The FUT2 (secretor) and FUT3 (Lewis) genes have been shown to be associated with some symptomatic enteric infections in both children and adults. These genes are responsible for the presence of histo-blood group antigens (HBGAs) in various secretions and epithelial surfaces.We evaluated whether the secretor and Lewis status influences asymptomatic enteric infections and thus EE severity on duodenal biopsies of stunted children. In this case-control study, we used saliva samples to determine the secretor and Lewis status of stunted children (cases, n = 113) enrolled in a nutritional rehabilitation program and from their well-nourished counterparts (controls, n = 42). Where available, saliva was also collected from the mothers. Baseline stool samples were used to detect asymptomatic enteropathogen carriage. Duodenal biopsies were collected from a subgroup of stunted children (n = 77) who had an upper gastrointestinal endoscopy done as part of the evaluation process for their non-response to nutritional therapy. The proportion of secretors was similar between the cases and the controls (82% vs 81%, P = 0.81). The stunted children had significantly higher rates of carrying multiple enteropathogens, but this was not associated with their secretor status nor that of their mothers. The secretor status was also not associated with mucosal morphometry of duodenal biopsies. This case-control analysis in Zambian children does not support the hypothesis that fucosylation status determines asymptomatic enteropathogen carriage in stunting.

Predisposition of Blood group Non-secretors to Urinary tract infection with Escherichia coli Anti-microbial Resistance and Acute Kidney Injury

Urinary tract infection (UTI) causes significant renal damage and disease severity is compounded by antimicrobial resistance (AMR) and other comorbidities in the patient. Blood group antigens secreted in body fluids (secretor status) are known to play a role in bacterial adhesion and we studied its influence on AMR in UTI. A total of 2758 patients with UTI were studied with urine culture, qualitative and semiquantitative urine microscopy, serum creatinine and secretor status in saliva samples by adsorption-inhibition method. Of these, AMR from 300 patients with E. coli infection were assessed as per CLSI 2019 guidelines and extended-spectrum beta-lactamase (ESBL) genes (bla TEM, bla CTX-M, bla SHV) and NDM1 genes were studied using TaqMan probes in Real-time polymerase chain reaction. Patients with UTI were followed up for two weeks. Female patients had higher predilection (57%) for E. coli infection while patients with diabetes or non-secretors had none. In our study, ESBL producers were seen in 62% of the E. coli isolates and fosfomycin had 100% susceptibility. Non-secretors were significantly associated with acute kidney injury (AKI), AMR and ESBL genes. Multidrug-resistance (MDR) was noted in 127/160 (79.4%) ESBL and 17/18 (94%) NDM1 gene encoding strains. Quantitative urine microscopy scoring predicted AKI both at presentation and at end of follow up. ESBL producers were common in our study population and non-secretors had a significant association with AMR genes. Urine microscopy scoring system may be a useful tool to predict AKI in patients with UTI.

Longitudinal changes of human milk oligosaccharides, breastmilk microbiome and infant gut microbiome are associated with maternal characteristics

AbstractHuman milk oligosaccharides (HMOs) play an important role in infant health. This study aimed to investigate the association of maternal characteristics with HMOs, human breastmilk (HBM) microbiome and infant gut microbiome over the first three months of lactation. Chinese mothers and infant pairs (n = 110) were included in this prospective cohort. Secretor status linked with α1,2‐fucosyltransferase expression was determined by the presence of total α1,2‐fucosylated HMOs in HBM for 75.8% of the mothers. The concentration of dominant HMOs significantly decreased over three months except for 3’‐fucosyllactose. In addition to the elevated levels of α1,2‐fucosylated HMOs, other neutral HMOs significantly reduced in secretors milk. Alpha‐diversity of HBM and infant gut microbiome significantly increased over time, and an elevated abundance of Bifidobacterium and decreased levels of Streptococcus, Staphylococcus and Clostridium in the infant gut microbiota were noted. Multi‐association analysis indicated maternal age and body mass index significantly correlated with specific HMOs and infant growth. Our study provides pivotal data on Chinese HMOs distribution profile, and their association with maternal characteristics and the infant gut microbiome.

Analysis of blood group antigens on MUC5AC in mucinous ovarian cancer tissues using in situ proximity ligation assay.

MUC5AC has been indicated to be a marker for mucinous ovarian cancer (OC). We investigated the use of in situ proximity ligation assay (PLA) for blood group ABH expressing MUC5AC to differentiate between serous and mucinous OC, to validate preceding observations that also MUC5AC ABH expression is increased in mucinous OC. We developed PLA for anti-A, B, and H/anti-MUC5AC and a PLA using a combined lectin Ulex europaeus agglutinin I (UEA I)/anti-MUC5AC assay. The PLAs were verified with mass spectrometry, where mucinous OC secretor positive patients’ cysts fluids containing ABH O-linked oligosaccharides also showed positive OC tissue PLA staining. A nonsecretor mucinous OC cyst fluid was negative for ABH and displayed negative PLA staining of the matched tissue. Using the UEA I/MUC5AC PLA, we screened a tissue micro array of 410 ovarian tissue samples from patients with various stages of mucinous or serous OC, 32 samples with metastasis to the ovaries and 34 controls. The PLA allowed differentiating mucinous tumors with a sensitivity of 84% and a specificity of 97% both against serous cancer but also compared to tissues from controls. This sensitivity is close to the expected incidence of secretor individuals in a population. The recorded sensitivity was also found to be higher compared to mucinous type cancer with metastasis to the ovaries, where only 32% were positive. We conclude that UEA 1/MUC5AC PLA allows glycospecific differentiation between serous and mucinous OC in patients with positive secretor status and will not identify secretor negative individuals with mucinous OC.

The Mean of Milk: A Review of Human Milk Oligosaccharide Concentrations throughout Lactation.

Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother’s genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0–5 days), transitional milk (6–14 days), mature milk (15–90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother’s ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2′-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2′-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6′-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3′-SL, LST c, and TF-LNH.

Lewis and ABO histo‐blood types and the secretor status of patients hospitalized with COVID‐19 implicate a role for ABO antibodies in susceptibility to infection with SARS‐CoV‐2

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) targets the respiratory and gastric epithelium, causing coronavirus disease 2019 (COVID‐19). Tissue antigen expression variations influence host susceptibility to many infections. This study aimed to investigate the closely linked Lewis (FUT3) and ABO histo‐blood types, including secretor (FUT2) status, to infections with SARS‐CoV‐2 and the corresponding severity of COVID‐19.Study Design and MethodsPatients (Caucasians, n = 338) were genotyped for ABO, FUT3, and FUT2, and compared to a reference population of blood donors (n = 250,298). The association between blood types and severity of COVID‐19 was addressed by dividing patients into four categories: hospitalized individuals in general wards, patients admitted to the intensive care unit with and without intubation, and deceased patients. Comorbidities were considered in subsequent analyses.ResultsPatients with blood type Lewis (a−b−) or O were significantly less likely to be hospitalized (odds ratio [OR] 0.669, confidence interval [CI] 0.446–0.971, OR 0.710, CI 0.556–0.900, respectively), while type AB was significantly more prevalent in the patient cohort (OR 1.519, CI 1.014–2.203). The proportions of secretors/nonsecretors, and Lewis a+ or Lewis b+ types were consistent between patients and controls. The analyzed blood groups were not associated with the clinical outcome as defined.DiscussionBlood types Lewis (a−b−) and O were found to be protective factors, whereas the group AB is suggested to be a risk factor for COVID‐19. The antigens investigated may not be prognostic for disease severity, but a role for ABO isoagglutinins in SARS‐CoV‐2 infections is strongly suggested.

A one-year study of human milk oligosaccharide profiles in the milk of healthy UK mothers and their relationship to maternal FUT2 genotype.

Human milk oligosaccharides (HMOs) are indigestible carbohydrates with prebiotic, pathogen decoy and immunomodulatory activities that are theorized to substantially impact infant health. The objective of this study was to monitor HMO concentrations over 1 year to develop a long-term longitudinal dataset. HMO concentrations in the breast milk of healthy lactating mothers of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) were measured at birth, 2weeks, 6weeks, 3months, 6months and 12months postpartum. HMO quantification was conducted by high-performance anion-exchange chromatography with pulsed amperometric detection using a newly validated "dilute-and-shoot" method. This technique minimizes sample losses and expedites throughput, making it particularly suitable for the analysis of large sample sets. Varying patterns of individual HMO concentrations were observed with changes in lactation timepoint and maternal secretor status, with the most prominent temporal changes occurring during the first 3months. These data provide valuable information for the development of human milk banks in view of targeted distribution of donor milk based on infant age. Maternal FUT2 genotype was determined based on identification at single-nucleotide polymorphism rs516246 and compared with the genotype expected based on phenotypic markers in the HMO profile. Surprisingly, two mothers genotyped as secretors produced milk that displayed very low levels of 2'-fucosylated moieties. This unexpected discrepancy between genotype and phenotype suggests that differential enzyme expression may cause substantial variation in HMO profiles between genotypically similar mothers, and current genotypic methods of secretor status determination may require validation with HMO markers from milk analysis.

Effect of Donor and Recipient ABH-Secretor Status on ABO-Incompatible Living Donor Kidney Transplantation

IntroductionABO blood group antigens within grafts are continuously exposed to anti-A/B antibodies in the serum of recipients after ABO-incompatible (ABOi) kidney transplantation and are instrumental in antibody-mediated rejection. Some individuals secrete soluble blood group antigens into body fluids. In this study, we investigated the effect of donor and recipient secretor status on the outcomes of ABOi kidney transplantation.MethodsData of a total of 32 patients with ABOi living donor kidney transplantation were retrospectively collected between 2014 and 2020 in West China Hospital. The genotype and phenotype of both donors and recipients were examined and evaluated with post-transplantation anti-A/B titer changes, graft function, and rejection.ResultsOf the 32 recipients and 32 donors, 23 (71.9%) recipients and 27 (84.4%) donors had secretor genotypes, whereas 9 (28.1%) recipients and 5 (15.6%) donors did not. Anti-A/B titers after ABOi kidney transplantation were not significantly influenced by the secretor status of either donors or recipients. The post-transplantation serum creatinine (Scr) levels and estimated glomerular filtration rate (eGFR) was better in weak- or non-secretor recipients at day 30 (Scr P = 0.047, eGFR P = 0.008), day 90 (Scr P = 0.010, eGFR P = 0.005), and month 9 (eGFR P = 0.008), and recipients from secretor donors had a lower incidence of graft rejection in the first year after ABOi transplantation (P = 0.004).ConclusionsA weak secretor status phenotype was found in both genotypes, i.e., individuals who secreted soluble antigens as well as those who did not. The recipient ABH-secretor status may have an influence on early posttransplant renal function, and the donor ABH-secretor status might affect the incidence of graft rejection.

Effect of Infant and Maternal Secretor Status on Rotavirus Vaccine Take-An Overview.

Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of α-1,2 fucosylated blood group antigens in mucosa and secretions, yielding the secretor-positive phenotype. Secretors are more susceptible to infection with predominant rotavirus genotypes, as well as to the commonly used live rotavirus vaccines. Difference in susceptibility to the vaccines is one proposed factor for the varying degree of efficacy observed between countries. Besides infection susceptibility, secretor status has been found to modulate rotavirus specific antibody levels in adults, as well as composition of breastmilk in mothers and microbiota of the infant, which are other proposed factors affecting rotavirus vaccine take. Here, the known and possible effects of secretor status in both infant and mother on rotavirus vaccine take are reviewed and discussed.

Human genomics of the humoral immune response against polyomaviruses.

Human polyomaviruses are widespread in humans and can cause severe disease in immunocompromised individuals. To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G responses against BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), Merkel cellpolyomavirus (MCPyV), WU polyomavirus (WUPyV), and human polyomavirus 6 (HPyV6) in 15,660 individuals of European ancestry from three independent studies. We observed significant associations for all tested viruses: JCPyV, HPyV6, and MCPyV associated with human leukocyte antigen class II variation, BKPyV and JCPyV with variants in FUT2, responsible for secretor status, MCPyV with variants in STING1, involved in interferon induction, and WUPyV with a functional variant in MUC1, previously associated with risk for gastric cancer. These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.

Secretor status prevents individuals from Helicobacter pylori infection

ABO antigens are not only present on the surface of red blood cells but are also secreted in body fluids. Individuals who can secrete these antigens in body fluids are called secretors while those who cannot are known as non-secretors. As compared to secretor non-secretors are at high risk to different bacterial, heart and autoimmune diseases but it is not clear that secretor status has an association with Helicobacter pylori. Therefore, this study was conducted to determine the secretor and non-secretor status in Helicobacter pylori infected patients. This cross-sectional study was carried out at Institute of Paramedical Sciences, Khyber Medical University Peshawar. A total of 192 samples were included in this study, 96 from Helicobacter pylori infected patients and 96 as a control group. Saliva samples were taken for the determination of secretor and non-secretor status by using Absorption inhibition method. Blood samples were obtained for ABO blood grouping and Helicobacter pylori determination. Out of 96 Helicobacter pylori infected patients, 36 (37.5%) were found as secretors and 60 (62.5%) were found as non-secretors while in normal individuals, secretors were 67 (69.8%) and non-secretors were 29 (30.2%). In H. pylori infected patients, classification of various ABH blood groups like A, B, AB and O were 24 (25%), 33 (34.3%), 18 (18.8%) and 21 (21.9%) respectively. In normal individuals’ the frequency of ABO was 28 (29.2%) of A, 28 (29.2%) of B, 8 (8.3%) of AB and 32 (33.3%) of O blood groups respectively. It is concluded that Helicobacter pylori infected patients have lowest secretor and highest non-secretors, because ABH antigens present in the body fluids of secretor show resistance to Helicobacter pylori infection. Moreover, non-secretors are more susceptible to bacterial infections. And it is known that Helicobacter pylori is a bacterium which can cause bacterial infections like gastric ulcer and duodenal ulcer. While normal individuals have highest secretor and lowest non-secretor status. Keywords: ABO blood groups; Body fluids; Helicobacter pylori; Non-secretor http://dx.doi.org/10.19045/bspab.2021.100053