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1.
Chest ; 162(3): 556-568, 2022 09.
Article in English | MEDLINE | ID: mdl-35271841

ABSTRACT

BACKGROUND: Twenty-five percent to 45% of COPD is caused by exposures other than active smoking. Secondhand tobacco smoke (SHS) has been suggested as an independent cause of COPD, based on its association with increased respiratory symptoms and a small decrease in lung function, but its impact on respiratory health and lung function after exposure cessation has not been explored. RESEARCH QUESTION: What are the consequences of airline SHS exposure on respiratory health and lung function decades after cessation? STUDY DESIGN AND METHODS: We performed a cohort study involving flight attendants because of their exposure to SHS that stopped > 20 years ago. We included subjects ≥ 50 years of age with > 1 year vs ≤ 1 year of airline SHS exposure (ie, exposed vs unexposed). Respiratory quality of life, as determined by the St. George's Respiratory Questionnaire (SGRQ), was the primary outcome for respiratory health. Key secondary outcomes included general quality of life (the Rand Corporation modification of the 36-item Short Form Health Survey Questionnaire; RAND-36), respiratory symptoms (COPD Assessment Test; CAT), and spirometry. RESULTS: The study enrolled 183 SHS-exposed and 59 unexposed subjects. Exposed subjects were 66.7 years of age, and 90.7% were female. They were hired at 23.8 years of age, were exposed to airline SHS for 16.1 years, and stopped exposure 27.5 years before enrollment. Prior SHS exposure was associated with worsened SGRQ (6.7 units; 95% CI, 2.7-10.7; P = .001), RAND-36 physical and social function, and CAT vs unexposed subjects. SHS exposure did not affect prebronchodilator spirometry or obstruction, but was associated with lower postbronchodilator FEV1 and FEV1/FVC, total lung capacity, and diffusing capacity of the lungs for carbon monoxide in a subset of subjects. Former smoking and SHS exposure synergistically worsened SGRQ (ß = 8.4; 95% CI, 0.4-16.4; P = .04). SHS exposure in people who never smoked replicated primary results and was associated with worsened SGRQ vs unexposed people (4.7 units; 95% CI, 0.7-7.0; P = .006). INTERPRETATION: Almost three decades after exposure ended, airline SHS exposure is strongly and dose-dependently associated with worsened respiratory health, but less robustly associated with airflow abnormalities used to diagnose COPD.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Tobacco Smoke Pollution , Cohort Studies , Female , Humans , Lung , Male , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/etiology , Quality of Life , Tobacco Smoke Pollution/adverse effects
2.
PLoS One ; 13(8): e0202901, 2018.
Article in English | MEDLINE | ID: mdl-30142173

ABSTRACT

Hyperuricemia is highly prevalent and especially common in subjects with metabolic, cardiovascular and renal diseases. In chronic kidney disease, hyperuricemia is extremely common, and uric acid (UA) excretion relies on gut uricolysis by gut microbiota. Current therapy for lowering serum UA includes drugs that may produce undesired secondary effects. Therefore, this pilot study was designed to evaluate the potential of two probiotic supplements to reduce systemic uric acid concentrations. Secondary objectives were to assess whether the hypouricemic effect related to a therapeutic benefit on the hyperuricemia-induced renal damage and hypertension. Analysis of fecal microbiota was also performed. Groups of 6 rats each were followed for 5 weeks and allocated in the following treatment groups: C = Control; HU-ND = Oxonic acid-induced hyperuricemia (HU) +regular diet; HU-P = HU+placebo; HU-F1 = HU+ probiotics formula 1 and HU-F2 = HU+ probiotics formula 2. We confirmed that oxonic acid-induced hyperuricemia produced hypertension and renal functional and structural changes, along with modest changes in the overall composition of fecal microbiota. Both probiotic-containing diets prevented HU, elevated UA urinary excretion and intrarenal UA accumulation induced by oxonic acid. The hypouricemic effect conferred by probiotic supplementation also prevented the renal changes and hypertension caused by hyperuricemia. However, probiotic treatment did not restore the fecal microbiota. In conclusion, we demonstrated for the first time the ability of probiotics containing uricolytic bacteria to lower serum uric acid in hyperuricemic animals with beneficial consequences on blood pressure and renal disease. As probiotics supplements are innocuous for human health, we recommend clinical studies to test if probiotic supplements could benefit hyperuricemic individuals.


Subject(s)
Dietary Supplements , Hyperuricemia/chemically induced , Hyperuricemia/prevention & control , Kidney/drug effects , Kidney/injuries , Oxonic Acid/adverse effects , Probiotics/pharmacology , Animals , Cytoprotection/drug effects , Dose-Response Relationship, Drug , Hyperuricemia/metabolism , Hyperuricemia/pathology , Kidney/metabolism , Kidney/pathology , Male , Oxidative Stress/drug effects , Pilot Projects , Rats , Rats, Wistar , Uric Acid/metabolism
3.
Open Forum Infect Dis ; 4(1): ofx020, 2017.
Article in English | MEDLINE | ID: mdl-28480290

ABSTRACT

BACKGROUND: Infection causes 1 of every 5 neonatal deaths globally. Group B Streptococcus (GBS) is the most significant pathogen, although little is known about its epidemiology and risk in low-income countries. METHODS: A cross-sectional study in 2015 at a public hospital in Guatemala City enrolled women ≥35 weeks' gestation. Vaginal and rectal swabs were processed using Lim broth and GBS CHROMagar then agglutination testing. Risk factors were assessed using multivariate analysis. Vaginal microbiota were profiled by 16S ribosomal ribonucleic acid sequencing in a subset of 94 women. RESULTS: Of 896 pregnant women, 155 (17.3%; 95% confidence interval [CI], 14.9-19.9) were GBS colonized. Colonization was associated with history of previous infant with poor outcome (odds ratio [OR], 1.94; 95% CI, 1.15-3.27) and increasing maternal age (OR, 1.05; 95% CI, 1.02-1.09). Multiparity was protective (OR, .39; 95% CI, .21-.72). Four (6%) GBS-exposed infants had early-onset neonatal sepsis. Vaginal microbiome composition was associated with previous antibiotic exposure (P = .003) and previous low birth weight infant (P = .03), but not GBS colonization (P = .72). Several individual taxa differed in abundance between colonized and noncolonized women. CONCLUSIONS: Group B Streptococcus is prevalent in pregnant women from Guatemala with different risk factors than previously described. Although the vaginal microbiome was not altered significantly in GBS-colonized women, use of antibiotics had an effect on its composition.

4.
Int Forum Allergy Rhinol ; 7(1): 16-23, 2017 01.
Article in English | MEDLINE | ID: mdl-27627048

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial inflammatory airway disorder in which bacteria are implicated in the initiation and/or sustenance of disease in some patients. The sinuses are colonized by bacteria even in health, and the potential for sinus-specific niches harboring unique microbial consortia raises questions for clinical and research investigation. The objective was to determine the degree to which resident upper airways microbiota differ between individuals and anatomic sites, in order to determine the optimal site of microbial sampling for study in CRS. METHODS: Eight CRS patients undergoing primary surgery were sampled bilaterally at the anterior nares, middle meatus, nasopharynx, maxillary sinus, frontal sinus, and sphenoid sinus for investigation using broad-range bacterial 16S ribosomal RNA (rRNA) sequencing. RESULTS: Between-subject variability in bacterial microbiota was substantially greater than within-subject variability. The middle meatus was fairly representative of the underlying sinuses, although corynebacteria were detected at higher abundances in the middle meatus, relative to the maxillary (p < 0.1), frontal (p < 0.05), or sphenoid (p < 0.1) sinuses. CONCLUSION: Interpersonal variation of the upper airway microbiome greatly outweighs niche-specific differences. The middle meatus is a fair representation of the underlying sinuses and may be considered for use as a simple single site for sampling in longitudinal studies or in subjects who have not undergone sinus surgery.


Subject(s)
Microbiota , Paranasal Sinuses/microbiology , Rhinitis/microbiology , Sinusitis/microbiology , Adult , Aged , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Chronic Disease , Female , Humans , Male , Middle Aged , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics
5.
J Pediatr Gastroenterol Nutr ; 63(3): 379-85, 2016 09.
Article in English | MEDLINE | ID: mdl-27548249

ABSTRACT

BACKGROUND: Iron therapy induces inflammation, which could decrease iron absorption. Increased exposure of iron in the gut could also alter microbiome file. Providing antioxidants such as vitamin E with iron therapy has been associated with reduced oxidative potential. OBJECTIVE: The aim of the present study was to test the efficacy of adding vitamin E to therapeutic iron therapy on iron repletion, inflammation markers, and gut microbiome in iron-deficient infants and toddlers. DESIGN: This was a randomized, double-blind, control trial in which infants and toddlers (Denver, CO metro area) who were at risk of iron deficiency were screened. Eligible participants were randomized to receive iron therapy (6 mg ·â€Škg ·â€Šday) plus placebo (n = 22) or iron (6 mg ·â€Škg ·â€Šday) and vitamin E (18 mg/day, n = 14) for 8 weeks. Iron and inflammation status, and gut microbiome (16S sequencing) were analyzed in all participants before and after the treatment. RESULTS: After 8 weeks of treatment, average serum ferritin level returned to normal for both iron + placebo and iron + vitamin E groups at 33.3 ±â€Š20.2 and 33.5 ±â€Š21.5 µg/L, respectively. Serum vitamin E concentration increased in iron + vitamin E group. No change over time was observed regarding serum interleukin-4, tumor necrosis factor-α, or fecal calprotectin. The relative abundance of the genus Roseburia (phylum Firmicutes), a butyrate producer, increased in the Fe + E group (Δ1.3%, P < 0.01). Also at the genus level, the genus Escherichia decreased by 1.2% on average among all participants (effect of time P = 0.01). CONCLUSIONS: Using a therapeutic iron dose of 6 mg ·â€Škg ·â€Šday is effective in treating iron deficiency during an 8-week period, without inducing persistent inflammatory response. Changes of the gut microbiome raised the possibility that antioxidant therapy in conjunction with therapeutic iron supplementation could potentially improve microbial community profiles in the intestinal tract.


Subject(s)
Anemia, Iron-Deficiency/drug therapy , Antioxidants/therapeutic use , Gastrointestinal Microbiome , Iron/administration & dosage , Vitamin E/administration & dosage , Anemia, Iron-Deficiency/microbiology , Child, Preschool , Dietary Supplements , Double-Blind Method , Female , Ferritins/blood , Humans , Infant , Male , RNA, Ribosomal, 16S/genetics , Vitamin E/blood
6.
J Pediatr Gastroenterol Nutr ; 63(3): 320-8, 2016 09.
Article in English | MEDLINE | ID: mdl-27035381

ABSTRACT

OBJECTIVES: Bacterial colonization and succession of the human intestine shape development of immune function and risk for allergic disease, yet these processes remain poorly understood. We investigated the relations between delivery mode, initial bacterial inoculation of the infant oropharynx (OP), and intestinal colonization. METHODS: We prospectively collected maternal rectal and vaginal swabs, infant OP aspirates, and infant stool from 23 healthy mother/infant pairs delivering by cesarean (CS) or vaginal delivery (VD) in an academic hospital. Bacterial abundance (16S rRNA sequencing) and community similarity between samples were compared by delivery mode. Shotgun DNA metagenomic sequencing of infant stool was performed. RESULTS: VD infants had higher abundance of Firmicutes (mainly lactobacilli) in OP aspirates whereas CS OP aspirates were enriched in skin bacteria. OP aspirates were more similar to maternal vaginal and rectal microbiomes in VD compared with CS. Bacteroidetes were more abundant through 6 weeks in stool of VD infants. Infant fecal microbiomes in both delivery groups did not resemble maternal rectal or vaginal microbiomes. Differences in fecal bacterial gene potential between CS and VD at 6 weeks clustered in metabolic pathways and were mediated by abundance of Proteobacteria and Bacteroidetes. CONCLUSIONS: CS infants exhibited different microbiota in the oral inoculum, a chaotic pattern of bacterial succession, and a persistent deficit of intestinal Bacteroidetes. Pioneer OP bacteria transferred from maternal vaginal and intestinal communities were not prominent constituents of the early infant fecal microbiome. Oral inoculation at birth may impact the intestinal microenvironment, thereby modulating early succession of intestinal bacteria.


Subject(s)
Delivery, Obstetric/methods , Feces/microbiology , Intestines/microbiology , Microbiota , Pharynx/microbiology , Adult , Delivery, Obstetric/adverse effects , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Prospective Studies , Rectum/microbiology , Sequence Analysis, DNA , Skin/microbiology , Vagina/microbiology
7.
Int Forum Allergy Rhinol ; 6(8): 800-6, 2016 08.
Article in English | MEDLINE | ID: mdl-26990369

ABSTRACT

BACKGROUND: Saline nasal irrigation is effective in the treatment of sinonasal disorders, including chronic rhinosinusitis (CRS). Despite bacterial contamination in rinse bottles and reports of infections from contaminated irrigation water, tap water is still used by ∼50% of irrigation users, raising a potential public health concern. This study aimed to determine whether bacteria from the water supply used in sinus irrigations colonizes the paranasal sinuses. METHODS: Samples were taken from the: (1) water used for irrigation, (2) faucet or container the water originated from, (3) rinse bottle, and (4) postoperative ethmoid cavity from 13 subjects with CRS. Microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to assess similarity in microbiota between samples, and genomic analysis was performed to assess clonality of cultured bacteria. RESULTS: Of 13 subjects, 6 used distilled water, 6 used tap water, and 1 used well water in this institutional review board (IRB)-approved observational study. Well-water had markedly more bacteria than tap or distilled water. There was a trend toward tap having more bacteria than distilled water. The sinus samples were notably dissimilar to the bottle, faucet, and irrigant (M-H 0.15, 0.09, and 0.18, respectively). There was no difference in postoperative microbiotas between distilled and tap water users. CONCLUSION: The current study suggests that irrigation plays little role in establishing the sinus microbiome. Although rinsing with tap water may never be formally recommended, these data are useful to counsel patients who prefer to do so in non-endemic areas if the municipal water supply is appropriately treated.


Subject(s)
Bacteria/isolation & purification , Paranasal Sinuses/microbiology , Therapeutic Irrigation , Bacteria/genetics , Equipment Contamination , Humans , Microbiota/genetics , RNA, Bacterial/analysis , RNA, Ribosomal, 16S/analysis , Therapeutic Irrigation/instrumentation , Water Microbiology
8.
Int Forum Allergy Rhinol ; 6(1): 34-40, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26388320

ABSTRACT

BACKGROUND: Endoscopic sinus surgery (ESS) enjoys high success rates, but repopulation with pathogenic bacteria is 1 of the hallmarks of poorer outcomes. There are many hypothesized sources of repopulating bacteria; however, this process remains largely unexplored. This study examined changes in the sinus microbiome after ESS and medical therapies to identify potential sources for postsurgical microbial repopulation. METHODS: Samples from the anterior nares, ethmoid sinus, and nasopharynx were taken at the time of surgery from 13 subjects undergoing ESS for chronic rhinosinusitis (CRS). Patients were treated postoperatively with 2 weeks of oral antibiotics and saline rinses. The ethmoid sinus was sampled at 2 and 6 weeks postoperatively; microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to compare similarity between samples. RESULTS: The bacterial burden of the ethmoid was higher 2 weeks postoperatively than 6 weeks postoperatively (p = 0.01). The 6-week samples most closely represented the anterior nares and ethmoid at surgery (M-H = 0.58 and 0.59, respectively), and were least similar to the nasopharynx (M-H = 0.28). Principal coordinates analysis (PCoA) plots illustrate that the ethmoid microbiota temporarily shifted after surgery and antibiotics but returned toward baseline in many subjects. CONCLUSION: Bacterial communities colonizing the ethmoid 6 weeks postoperatively were most similar to anterior nasal cavity and pretreatment sinus microbial profiles, indicating a high degree of resilience in the sinonasal microbiome of most subjects. Interestingly, surgery and postoperative antibiotic therapy does not appear to reduce bacterial burden, but rather, shifts the microbial consortia.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Ethmoid Sinus/microbiology , Microbiota , Nasopharynx/microbiology , Rhinitis/surgery , Sinusitis/surgery , Adult , Aged , Antibiotic Prophylaxis/adverse effects , Chronic Disease , Cross-Sectional Studies , Endoscopy , Female , Humans , Male , Middle Aged , Perioperative Care/adverse effects , Perioperative Care/methods , Rhinitis/microbiology , Sinusitis/microbiology , Surgical Wound Infection/prevention & control , Treatment Outcome
10.
Int Forum Allergy Rhinol ; 5(11): 981-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26272413

ABSTRACT

BACKGROUND: Although cigarette smoking aggravates chronic rhinosinusitis (CRS), a detailed examination of the sinus microbiota in CRS and its clinical subtypes has yet to be performed in relation to history of smoking. Consequently, we examined associations between smoking history and sinonasal microbiome alterations in both CRS and non-CRS populations. METHODS: Middle meatus swabs collected during endoscopic sinus surgery were analyzed by analysis of 16S ribosomal RNA (rRNA) sequences. Multiple analysis of variance tests were performed to determine whether microbiome composition varied with smoking history and other clinical/demographic covariates associated with CRS subtypes. RESULTS: A total 70 CRS patients and 31 control subjects were analyzed. In a univariate analysis, smoking (p = 0.04), preoperative antibiotics (p = 0.03), and purulence (p = 0.0002) were significantly associated with the genus-level composition of the middle meatus microbiota. When included in a multivariable model, smoking was found to have significant interactions with CRS (p = 0.02), polyposis (p = 0.03), purulence (p = 0.0004), and use of saline rinses (p = 0.05). Diverse bacterial taxa differed significantly in abundance between never-smokers and current/former smokers, as well as between different CRS subtypes. CONCLUSION: Substantial changes in sinus bacterial colonization were observed in smokers and nonsmokers. Although the microbiota of both CRS and non-CRS subjects were altered with smoking history, different bacterial taxa were affected by smoking in the 2 patient groups. Thus, the effects of smoking on the sinus microbiota are likely to be modified by physiological and immunological functions of the underlying sinus mucosa.


Subject(s)
Bacteria/genetics , Bacterial Infections/microbiology , Nasal Cavity/microbiology , RNA, Ribosomal, 16S/genetics , Rhinitis/microbiology , Sinusitis/microbiology , Smoking/adverse effects , Adult , Chronic Disease , Female , Humans , Male , Microbiota , Middle Aged , Species Specificity
11.
Diabetes ; 64(10): 3510-20, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26068542

ABSTRACT

We tested the hypothesis that alterations in the intestinal microbiota are linked with the progression of type 1 diabetes (T1D). Herein, we present results from a study performed in subjects with islet autoimmunity living in the U.S. High-throughput sequencing of bacterial 16S rRNA genes and adjustment for sex, age, autoantibody presence, and HLA indicated that the gut microbiomes of seropositive subjects differed from those of autoantibody-free first-degree relatives (FDRs) in the abundance of four taxa. Furthermore, subjects with autoantibodies, seronegative FDRs, and new-onset patients had different levels of the Firmicutes genera Lactobacillus and Staphylococcus compared with healthy control subjects with no family history of autoimmunity. Further analysis revealed trends toward increased and reduced abundances of the Bacteroidetes genera Bacteroides and Prevotella, respectively, in seropositive subjects with multiple versus one autoantibody. Canonical discriminant analysis suggested that the gut microbiomes of autoantibody-positive individuals and seronegative FDRs clustered together but separate from those of new-onset patients and unrelated healthy control subjects. Finally, no differences in biodiversity were evident in seropositive versus seronegative FDRs. These observations suggest that altered intestinal microbiota may be associated with disease susceptibility.


Subject(s)
Bacteria/classification , Diabetes Mellitus, Type 1/etiology , Gastrointestinal Microbiome/physiology , Islets of Langerhans/immunology , Adolescent , Adult , Autoantibodies/blood , Autoimmunity , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Disease Susceptibility , Feces/microbiology , Female , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/chemistry , RNA, Ribosomal, 16S/genetics , United States , Young Adult
12.
Int Forum Allergy Rhinol ; 5(1): 3-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25278448

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses in which bacteria are implicated. Culture-based assays are commonly used in clinical and research practice; however, culture conditions may not accurately detect the full range of microorganisms present in a sample. The objective of this study was to determine the accuracy of clinical culture of CRS specimens compared with DNA-based molecular techniques. METHODS: Ethmoid samples from 54 CRS patients collected during endoscopic sinus surgery were analyzed by both clinical culture and 16S ribosomal RNA (rRNA) gene sequencing. The association between 16S relative abundance and detection by culture was determined using logistic regression. RESULTS: Each subject had an average of 3 isolates identified by bacterial culture and 21.5 ± 12.5 species identified by 16S sequencing. On average, 1.6 dominant taxa (>10% abundance) per subject were identified using molecular techniques, but only 47.7% of these taxa were identified by culture. Low abundance taxa (abundance <1%) were detected in only 4.5% of cultures. The odds that any organism would be detected by culture were 2.3 times higher with each 10% increase in relative abundance (p < 0.01). Conversely, only 29.5% of isolates identified by culture represented the dominant species, whereas 40% accounted for species with 1% to 10% abundance. Interestingly, 12% of isolates detected by culture were not identified by 16S pyrosequencing. CONCLUSION: Standard clinical culture is a poor representation of resident microbiota. The incorporation of modern culture-independent techniques into clinical and research practices provides additional information that may be relevant for CRS.


Subject(s)
Bacteria/isolation & purification , Bacterial Infections/diagnosis , Paranasal Sinuses/microbiology , Rhinitis/diagnosis , Sinusitis/diagnosis , Adult , Bacterial Infections/complications , Bacterial Infections/microbiology , Chronic Disease , Colony Count, Microbial , Cross-Sectional Studies , Female , Humans , Male , Microbiota/genetics , Middle Aged , Molecular Typing , Observer Variation , Paranasal Sinuses/surgery , Predictive Value of Tests , RNA, Ribosomal, 16S/analysis , Rhinitis/complications , Rhinitis/microbiology , Sinusitis/complications , Sinusitis/microbiology
13.
Diabetes ; 63(2): 619-31, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24353176

ABSTRACT

RIP-B7.1 transgenic mice express B7.1 costimulatory molecules in pancreatic islets and develop diabetes after treatment with polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA and agonist of Toll-like receptor (TLR) 3 and retinoic acid-inducible protein I. We used this model to investigate the role of TLR pathways and intestinal microbiota in disease progression. RIP-B7.1 mice homozygous for targeted disruption of TLR9, TLR3, and myeloid differentiation factor-88 (MyD88), and most of the wild-type RIP-B7.1 mice housed under normal conditions remained diabetes-free after poly I:C administration. However, the majority of TLR9-deficient mice and wild-type animals treated with poly I:C and an antibiotic developed disease. In sharp contrast, TLR3- and MyD88-deficient mice were protected from diabetes following the same treatment regimen. High-throughput DNA sequencing demonstrated that TLR9-deficient mice treated with antibiotics plus poly I:C had higher bacterial diversity compared with disease-resistant mice. Furthermore, principal component analysis suggested that TLR9-deficient mice had distinct gut microbiome compared with the diabetes-resistant mice. Finally, the administration of sulfatrim plus poly I:C to TLR9-deficient mice resulted in alterations in the abundance of gut bacterial communities at the phylum and genus levels. These data imply that the induction of diabetes in the RIP-B7.1 model is critically dependent on TLR3 and MyD88 pathways, and involves modulation of the intestinal microbiota.


Subject(s)
Diabetes Mellitus/metabolism , Gene Expression Regulation/physiology , Intestines/microbiology , Myeloid Differentiation Factor 88/metabolism , Toll-Like Receptor 3/metabolism , Animals , Bacteria/classification , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Poly I-C , Toll-Like Receptor 3/genetics , Toll-Like Receptor 9/genetics , Toll-Like Receptor 9/metabolism
14.
J Pediatr ; 163(2): 416-23, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23452586

ABSTRACT

OBJECTIVE: To compare iron status in breastfed infants randomized to groups receiving complementary feeding regimens that provided iron from fortified infant cereals or meats, and to examine the development of the enteric microbiota in these groups. STUDY DESIGN: Forty-five exclusively breastfed 5-month-old infants were randomized to 1 of 3 feeding groups (FGs)-commercially available pureed meats, iron- and zinc-fortified infant cereals, or iron-only fortified infant cereals-as the first and primary complementary food through 9-10 months of age. Dietary iron was determined by monthly 3-day diet records. Iron status was assessed at the end of the study by measurements of hemoglobin, serum ferritin, and soluble transferrin receptor levels. In a subsample of 14 infants, enteric microbiota were profiled in monthly stool samples (5-9 months) by 16S ribosomal RNA gene pyrosequencing. RESULTS: Infants in the 2 cereal FGs had 2- to 3-fold greater daily iron intakes versus the meat FG (P < .0001). More than one-quarter (27%) of the infants had a low serum ferritin level, and 36% were mildly anemic, with no significant differences by FG; more infants in the meat FG had a high soluble transferrin receptor value (P = .03). Sequence analysis identified differences by time and FG in the abundances of several bacterial groups, including significantly more abundant butyrate-producing Clostridium group XIVa in the meat FG (P = .01) CONCLUSION: A high percentage of healthy infants who were breastfed-only were iron-deficient, and complementary feeding, including iron exposure, influenced the development of the enteric microbiota. If these findings are confirmed, then reconsideration of strategies to both meet infants' iron requirements and optimize the developing microbiome may be warranted.


Subject(s)
Breast Feeding , Gastrointestinal Tract/microbiology , Infant Food , Infant Nutritional Physiological Phenomena , Iron Deficiencies , Iron, Dietary/administration & dosage , Iron/blood , Metagenome , Humans , Infant , Nutritional Status
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