Human Milk Oligosaccharide Profiles and the Secretor and Lewis Gene Status of Indonesian Lactating Mothers.

Purpose: Human milk oligosaccharides (HMOs) may be genetically determined based on the secretor and Lewis status of the mother. This study aims to determine the HMO profile and the secretor and Lewis gene status of Indonesian lactating mothers. Methods: Baseline data of 120 mother-infant pairs between 0-4 months post-partum obtained from a prospective longitudinal study was used. The concentrations of 2'-fucosyllactose (2'FL), lacto-N-fucopentaose I (LNFP I), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 3'-sialyllactose (3'SL), and 6'-sialyllactose (6'SL) were measured. Genetic analysis was performed for mothers using targeted next-generation sequencing and Sanger sequencing. Wild-type AA with the rs1047781 (A385T) polymorphism was categorized as secretor positive, while heterozygous mutant AT was classified as a weak secretor. The presence of rs28362459 (T59G) heterozygous mutant AC and rs3745635 (G508A) heterozygous mutant CT genes indicated a Lewis negative status, and the absence of these genes indicated a positive status. Subsequently, breast milk was classified into various groups, namely Group 1: Secretor+Lewis+ (Se+Le+), Group 2: Secretor-Lewis+ (Se-Le+), Group 3: Secretor+Lewis- (Se+Le-), and Group 4: Secretor-Lewis- (Se-Le-). Data were analyzed using the Mann-Whitney and Kruskal-Wallis rank tests, and a p-value of 0.05 indicated statistical significance. Results: A total of 58.3% and 41.7% of the samples had positive and weak secretor statuses, respectively. The proportion of those in Group 1 was 85%, while 15% were Group 3. The results showed that only 2'FL significantly differed according to the secretor status (p-value=0.018). Conclusion: All Indonesian lactating mothers in this study were secretor positive, and most of them had a Lewis-positive status.

Human Milk Oligosaccharides as a Missing Piece in Combating Nutritional Issues during Exclusive Breastfeeding.

Extensive studies have shown that breast milk is the best source of nutrition for infants, especially during the first six months, because it fulfills almost all of their nutritional needs. Among the many functional building blocks in breast milk, human milk oligosaccharides (HMOs) have been receiving more attention recently. Furthermore, it is the third most common group of compounds in human milk, and studies have demonstrated the health benefits it provides for infants, including improved nutritional status. HMOs were previously known as the 'bifidus factor' due to their 'bifidogenic' or prebiotic effects, which enabled the nourishment of the gastrointestinal microbiota. Healthy gastrointestinal microbiota are intestinal health substrates that increase nutrient absorption and reduce the incidence of diarrhea. In addition, HMOs, directly and indirectly, protect infants against infections and strengthen their immune system, leading to a positive energy balance and promoting normal growth. Non-modifiable factors, such as genetics, and modifiable factors (e.g., maternal health, diet, nutritional status, environment) can influence the HMO profile. This review provides an overview of the current understanding of how HMOs can contribute to the prevention and treatment of nutritional issues during exclusive breastfeeding.

Dietary and Plasma Carboxymethyl Lysine and Tumor Necrosis Factor-α as Mediators of Body Mass Index and Waist Circumference among Women in Indonesia.

Dietary and plasma carboxymethyl lysine (dCML, pCML) and plasma tumor necrosis factor-α (pTNF-α) may be associated with obesity in affluent society. However, evidence in women from low-middle income countries with predominantly traditional diets is lacking. We investigated the mediator effects of dCML, pCML and pTNF-α on body mass index (BMI) and waist circumference (WC) among Indonesian women. A cross-sectional study was conducted among 235 non-diabetic, non-anemic and non-smoking women aged 19-50 years from selected mountainous and coastal areas of West Sumatra and West Java. Dietary CML, pCML, pTNF-α were obtained from 2 × 24-h recalls, ultra-performance liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay, respectively. Between-group differences were analyzed by the Chi-square or Mann-Whitney test and mediator effects by Structural Equation Modeling. The medians and interquartile-ranges of dCML, pCML and pTNF-α were 2.2 (1.7-3.0) mg/day, 22.2 (17.2-28.2) ng/mL and 0.68 (0.52-1.00) IU/mL, respectively, and significantly higher in the WC ≥ 80 cm than in the WC < 80 cm group, but not in BMI ≥ 25 kg/m2 compared to BMI < 25 kg/m2 group. Plasma CML and pTNF-α were positively and directly related to WC (ß = 0.21 [95% CI: 0.09, 0.33] and ß = 0.23 [95% CI: 0.11, 0.35], respectively). Dietary CML that correlated with dry-heat processing and cereals as the highest contributions was positively related to WC (ß = 0.33 [95% CI: 0.12, 0.83]). Ethnicity, level of education, intake of fat, and intake of energy contributed to dCML, pCML and pTNF-α, and subsequently affected WC, while only ethnicity contributed to BMI through dCML, pCML and pTNF-α (ß = 0.07 [95% CI: 0.01, 0.14]). A positive direct effect of dCML on pCML and of pCML and pTNF-α on WC was seen among Indonesian women. Dietary CML seems to have several paths that indirectly influence the increases in WC if compared to BMI. Thus, intake of CML-rich foods should be reduced, or the foods consumed in moderate amounts to avoid the risk of central obesity in this population.

Association of CYP2D6*10 (c. 100 C>T) Genotype with Z-END Concentration in Patients with Breast Cancer Receiving Tamoxifen Therapy in Indonesian Population.

BACKGROUND: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). OBJECTIVE: The purpose of the study was to determine the association between CYP2D6*10 (c.100C>T) genotype and attainment of the plasma steady-state Z-END minimal threshold concentration (MTC) in Indonesian women with breast cancer. METHODS: A cross-sectional study was performed in 125 ambulatory patients with breast cancer consuming TAM at 20 mg/day for at least 4 months. The frequency distribution of CYP2D6*10 (c.100C>T) genotypes (C/C: wild type; C/T: heterozygous mutant; T/T: homozygous mutant) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the results of which were subsequently confirmed by sequencing. The genotypes were categorized into plasma Z- END concentrations of <5.9 ng/mL and ≥5.9 ng/mL, which were measured using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). RESULTS: Percentages of C/C, CT, and T/T genotypes were 22.4%, 29.6%, and 48.8%, respectively. Median (25-75%) Z-END concentrations in C/C, C/T, and T/T genotypes were 9.58 (0.7-6.0), 9.86 (0.7-26.6), and 3.76 (0.9-26.6) ng/mL, respectively. Statistical analysis showed a significant difference in median Z-END concentration between patients with T/T genotype and those with C/C or C/T genotypes (p<0.001). There was a significant association between CYP2D6*10 (c.100C>T) genotypes and attainment of plasma steady-state Z-END MTC (p<0.001). CONCLUSION: There was a significant association between CYP2D6*10 (c.100C>T) and attainment of plasma steady-state Z-END MTC in Indonesian breast cancer patients receiving TAM at a dose of 20 mg/day.

Effect of soy isoflavone supplementation on endothelial dysfunction and oxidative stress in equol-producing postmenopausal women.

Dietary isoflavones are considered to be cardioprotective because of their structural similarity to estrogen. Equol is a metabolite of daidzein that is more potent than daidzein itself. The effect of equol on endothelial function and oxidative stress remains unclear. The objective of this study was to determine the effect of 100 mg/day soy isoflavone supplementation on the following markers: vascular cell adhesion molecule-1 (VCAM-1) and nitric oxide (NO) as markers of vascular endothelial function, and malonyldialdehyde (MDA) as oxidative stress marker in equol-producing postmenopausal women. A stratified randomized double blind controlled trial was conducted among 190 postmenopausal Indonesian women aged 47 to 60 years. They were stratified into equol producers and equol nonproducers. The random allocation of intervention was carried out separately in each stratum. The intervention group received tablets consisting of 100 mg soy isoflavones and calcium carbonate 500 mg, and the control group received 500 mg calcium carbonate. The concentrations of VCAM-1, NO and MDA were measured at baseline and post-supplementation at 6 months. After 6 months of supplementation the MDA concentrations were significantly lower in the soy-isoflavone equol producers compared with equol nonproducers (p=0.021). Similar results were also found for VCAM-1 and NO concentrations, but these were statistically not significant (p = 0.413 and p= 0.724, respectively). This study demonstrates that isoflavone supplementation in postmenopausal women with equol-producer status had a more beneficial effect by decreasing the MDA concentration, but did not improve VCAM-1 and NO concentrations.

Survey on gastrointestinal parasites and detection of Cryptosporidium spp. on cattle in West Java, Indonesia.

OBJECTIVE: To evaluate the presence of gastrointestinal parasites on cattle in Indonesia because the prevalence of parasites varies between countries depending on the terrain surrounding livestock farms and investigations in Indonesia have never been performed. METHODS: Fecal samples from cattle at 35 farms in 7 districts in West Java, Indonesia, has been examined using the floatation or sedimentation methods, and a immunofluorescence assay and experimentally inoculation to mice for Cryptosporidium or Giardia.spp. RESULTS: 153 of 394 examined cattle (38.8%) were infected with gastrointestinal parasites. The prevalence of Eimeria spp., Nematoda spp. (including Oesophagustomum and Bunostomum-like), Fasciola gigantica and Paramphistomum spp. was 22.4%, 11.2%, 12.5% and 3.8%, respectively. Cryptosporidium andersoni (C. andersoni) was also found in two samples. One isolate of this parasite was confirmed to be transmitted to mice, in contrast to the isolates from other countries. CONCLUSIONS: although this survey is preliminary, the results shows that the infection of gastrointestinal parasites in Indonesia was not high, but these infected cattle could be as a potential source leading to economic losses in livestock production.

Preventing low birthweight through maternal multiple micronutrient supplementation: a cluster-randomized, controlled trial in Indramayu, West Java.

BACKGROUND: Micronutrient deficiencies may contribute to a higher incidence of low birthweight (LBW). UNICEF/United Nations University/World Health Organization jointly proposed a formulation for a multiple micronutrient supplement for pregnant women, and several effectiveness trials were conducted to assess its impact. OBJECTIVE: To evaluate the efficacy of prenatal multiple micronutrient supplementation for improving birth size, pregnancy outcome, and maternal micronutrient status in comparison with iron-folic acid supplementation. METHODS: We carried out a cluster-randomized, controlled trial in Indramayu, Indonesia, involving 843 pregnant women. Of these, 432 received multiple micronutrients and 411 received iron-folic acid. Fieldworkers visited the women daily to observe supplement consumption and record fetal loss and mortality. RESULTS: The mean number of supplements consumed during pregnancy and 30 days postpartum was high (136 in the group receiving multiple micronutrients and 140 in the iron-folic acid group). The women consumed the supplements on average 5 days per week. Although there were no significant differences between the groups in the percentage of infants with LBW there was a trend toward a lower incidence of LBW in the group receiving multiple micronutrients (6.3% vs. 7.3%), and the mean birthweight was 40 g higher in the group receiving multiple micronutrients than in the iron-folic acid group, although the difference was not significant. Among those who consumed 90 or more supplements during pregnancy, women taking multiple micronutrients had a 3.3% combined rate of miscarriage, stillbirth, or neonatal death, as compared with 6.9% for those taking iron-folic acid only (p < .049). The anemia rates in the two groups were similar after supplementation, even though the amount of iron in the multiple micronutrient supplement was half that in the iron-folic acid supplement. Serum retinol was higher in the group receiving multiple micronutrients. CONCLUSIONS: Multivitamin supplementation use among pregnant women is as effective as iron-folic acid in improving anemia status and appears to have other benefits for maternal and child nutritional status.

Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia.

Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies.

Sex differences in prevalence of anaemia and iron deficiency in infancy in a large multi-country trial in South-East Asia.

To evaluate effects of Fe supplementation and sex on the prevalence of anaemia and Fe status in infants in South-East Asia, biochemical data from four parallel, randomized, double-blind trials with Fe and/or Zn supplementation in infants (n 2452) in Indonesia, Thailand and Vietnam was pooled. At recruitment (5 months of age), Hb concentrations were slightly but significantly lower in boy infants compared with girl infants (108.7 g/l v. 111.4 g/l, P = 0.04). At 11 months of age, boy infants not receiving Fe had significantly lower Hb (106.2 g/l v. 111.0 g/l, P < 0.001) and lower serum ferritin concentrations (14.3 microg/l v. 21.1 g/l, P < 0.001) than girl infants not receiving Fe. Consequently, boy infants had a relative risk of 1.6 (95% CI 1.3, 2.1) to be anaemic, and of 3.3 (95% CI 2.1, 5.0) for having Fe deficiency anaemia compared with girl infants. Fe supplementation significantly increased Hb concentrations in both boys and girls. There was no sex difference in Fe status in infants receiving Fe for 6 months. This study shows that the markedly higher risk for anaemia and Fe deficiency indicates higher Fe requirements in boy than in girl infants. In South-East Asia, standard infant feeding practices do not provide sufficient Fe to meet requirements of infants, especially boys. Current daily recommended intake for Fe in infancy is the same for boy and girl infants however. Our findings suggest that in especially the second half of infancy, Fe requirements for boy infants are approximately 0.9 mg/d higher than for girl infants.

Combined iron and zinc supplementation in infants improved iron and zinc status, but interactions reduced efficacy in a multicountry trial in southeast Asia.

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n=2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P<0.01) and zinc deficiency by 10% (P<0.05) but was less effective (P<0.05) than supplementation with either iron (28% reduction in anemia) or zinc alone (18% reduction in zinc deficiency). Iron reduced the effect of zinc supplementation (interaction P<0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-2.5 g/L, P<0.001), independent of iron supplementation (Pinteraction=0.25). The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls (effect size 12.0 vs. 6.8 g/L, respectively). In infants not receiving iron, VAC administration tended to be associated with lower (3.2%, P=0.07) hemoglobin concentrations. Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies. Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status. Furthermore, VAC administration in the absence of iron supplementation may increase the incidence of anemia.

Serovar distribution and antibiotic susceptibility of nontyphoidal Salmonella isolated from pediatric patients in Jakarta, Indonesia.

A study was conducted during January 2003 through August 2005, at two community health centers in south Jakarta, Indonesia, to detect nontyphoidal Salmonella infections in children with diarrhea. A total of 814 rectal swab samples were collected, of which 56 (6.9%) were positive for Salmonella. Among the serovars detected, Salmonella enterica serovar Typhimurium was found most frequently in 32.1% of all Salmonella isolates. Antimicrobial susceptibility testing using eight antibiotics showed 5.6% to 66.7% of Salmonella serovars resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, and nalidixic acid. However, all serovars were susceptible to norfloxacin, ciprofloxacin, and ceftriaxone.

Growth inhibition of enteric pathogens by zinc sulfate: an in vitro study.

OBJECTIVE: To determine the inhibition effect of zinc sulfate on isolates of enteric bacteria. MATERIALS AND METHODS: Mueller-Hinton agar containing different concentrations of zinc sulfate was prepared. Isolates used in this study were obtained from local clinics. They were Salmonella typhi, Salmonella groups A, B, C, D and E, Escherichia coli, Enterobacter, Shigella and Vibrio cholerae. Overnight cultures of test organisms in brain-heart infusion broth were adjusted to 0.5 McFarland standard turbidity by adding normal saline with 1 microl of each adjusted broth culture inoculated onto zinc sulfate agar plates. The plates were incubated for 18-20 h at 37 degrees C. The inhibition concentration was recorded as the lowest concentration of zinc sulfate that completely inhibited growth. RESULTS: All enteric pathogens tested were inhibited by zinc sulfate. Of the isolates, S. typhi was most sensitive since 20% of the strains were inhibited by zinc sulfate of 0.8 mg/ml. Salmonella paratyphi A was inhibited at 1.2 mg/ml. Other Salmonella spp. were inhibited at concentrations between 1.4 and 2.0 mg/ml. V. cholerae O1 and Shigella flexneri demonstrated a similar pattern of inhibition as S. paratyphi A. A higher concentration of zinc sulfate (1.6 mg/ml) was required to completely inhibit Shigella sonnei. CONCLUSION: The findings indicate that zinc sulfate has an antimicrobial effect on enteric pathogens and may contribute to the treatment of diarrhea.