Publications by authors named "Mark A McGuire"

91 Publications

Microbiomes and Childhood Malnutrition: What Is the Evidence?

Ann Nutr Metab 2021 Aug 30:1-13. Epub 2021 Aug 30.

Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, Idaho, USA.

Both undernutrition and overnutrition continue to represent enduring global health crises, and with the growing implications of both forms of malnutrition occurring simultaneously in individuals and populations (referred to as the double burden of malnutrition), understanding their biological and environmental causes is a primary research and humanitarian necessity. There is growing evidence of a bidirectional association between variation in the gastrointestinal (GI) microbiome and risk of/resilience to malnutrition during early life. For example, studies of siblings who discordantly do or do not develop severe malnutrition show clear differences in the diversity and composition of fecal microbiomes. These differences are transiently lessened during refeeding but re-emerge thereafter. These findings have been somewhat recapitulated using animal models, but small sample sizes and limited range complicate interpretation of results and applicability to humans. Mechanisms driving these differences are currently unknown but likely involve a combination of inflammatory pathways (and perhaps antioxidant status of the host) and effects on nutrient availability, requirements, and utilization by both host and microbe. A less robust literature also suggests that variation in GI microbiome is associated with risk for obesity during childhood. The putative impact of GI microbiomes on malnutrition is likely modified by a variety of important variables such as genetics (likely driven, in part, by evolution), environmental pathogen exposure and its timing, dietary factors, and cultural/societal pattern (e.g., use of antibiotics). Given the growing double burden of malnutrition, this topic demands a focused interdisciplinary approach that expands from merely characterizing differences and longitudinal changes in fecal microbes to examining their functionality during early life. Understanding the complex composition of human milk and how its components impact establishment and maintenance of the recipient infant's GI microbiome will also undoubtedly shed important light on this topic.
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http://dx.doi.org/10.1159/000519001DOI Listing
August 2021

Pumping supplies alter the microbiome of pumped human milk: An in-home, randomized, crossover trial.

Am J Clin Nutr 2021 Sep 12. Epub 2021 Sep 12.

Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.

Background: The human milk microbiome may contribute to the benefits of breastfeeding by providing bacteria to the infant gastrointestinal tract. Many women pump their milk, but the effect of pumping on the milk microbiome is unknown.

Objectives: Our objective was to determine the effects of pumping supplies on the pumped human milk microbiome.

Methods: This was an in-home, randomized, crossover trial of 2 collection methods. Women (n = 52) pumped twice within 3.5 h, once with their own breast pumps and milk collection supplies (OWN SUPP) and once with a hospital-grade pump and sterile collection supplies (STER SUPP). Pumping order was randomized. The milk microbiome was characterized by aerobic culturing and 16S ribosomal RNA gene sequencing.

Results: Milk collected with OWN SUPP yielded more total aerobic and gram-negative bacteria than milk collected with STER SUPP, reflecting a 6.6 (adjusted OR; 95% CI: 1.7, 25; P = 0.006) higher odds of containing >104 total aerobic CFU/mL and 19 (adjusted OR; 95% CI: 4.1, 88; P < 0.0001) higher odds of yielding culturable gram-negative bacteria. Milk collected with OWN SUPP yielded more Proteobacterias , including higher relative abundances of Acinetobacter and Stenotrophomonas, compared to milk collected with STER SUPP. Results were consistent across pumping-order groups.

Conclusions: We demonstrated that pumping supplies altered the milk microbiome. On average, milk collected with OWN SUPP resulted in elevated levels of culturable total and gram-negative bacteria and proteobacterial DNA compared to milk collected with STER SUPP. More research is needed to assess implications for infant health.
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http://dx.doi.org/10.1093/ajcn/nqab273DOI Listing
September 2021

Breastfeeding Beyond 12 Months: Is There Evidence for Health Impacts?

Annu Rev Nutr 2021 Jun 11. Epub 2021 Jun 11.

Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho 83844, USA; email:

Because breastfeeding provides optimal nutrition and other benefits for infants (e.g., lower risk of infectious disease) and benefits for mothers (e.g., less postpartum bleeding), health organizations recommend that healthy infants be exclusively breastfed for 4 to 6 months in the United States and 6 months internationally. Recommendations related to how long breastfeeding should continue, however, are inconsistent. The objective of this article is to review the literature related to evidence for benefits of breastfeeding beyond 1 year for mothers and infants. In summary, human milk represents a good source of nutrients and immune components beyond 1 year. Some studies point toward lower infant mortality in undernourished children breastfed for >1 year, and prolonged breastfeeding increases interbirth intervals. Data on other outcomes (e.g., growth, diarrhea, obesity, and maternal weight loss) are inconsistent, often lacking sufficient control for confounding variables. There is a substantial need for rigorous, prospective, mixed-methods, cross-cultural research on this topic. Expected final online publication date for the , Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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http://dx.doi.org/10.1146/annurev-nutr-043020-011242DOI Listing
June 2021

Variation in Human Milk Composition Is Related to Differences in Milk and Infant Fecal Microbial Communities.

Microorganisms 2021 May 27;9(6). Epub 2021 May 27.

Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID 83844, USA.

Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, as well as the associations among these factors and microbial community structures in milk and infant feces. Here, we characterized and contrasted concentrations of milk-borne lactose, protein, and HMOs, and examined their associations with milk and infant fecal microbiomes in samples collected in 11 geographically diverse sites. Although geographical site was strongly associated with milk and infant fecal microbiomes, both sample types assorted into a smaller number of community state types based on shared microbial profiles. Similar to HMOs, concentrations of lactose and protein also varied by geography. Concentrations of HMOs, lactose, and protein were associated with differences in the microbial community structures of milk and infant feces and in the abundance of specific taxa. Taken together, these data suggest that the composition of human milk, even when produced by relatively healthy women, differs based on geographical boundaries and that concentrations of HMOs, lactose, and protein in milk are related to variation in milk and infant fecal microbial communities.
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http://dx.doi.org/10.3390/microorganisms9061153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230061PMC
May 2021

Comparison of Two Approaches for the Metataxonomic Analysis of the Human Milk Microbiome.

Front Cell Infect Microbiol 2021 25;11:622550. Epub 2021 Mar 25.

Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain.

Recent work has demonstrated the existence of large inter-individual and inter-population variability in the microbiota of human milk from healthy women living across variable geographical and socio-cultural settings. However, no studies have evaluated the impact that variable sequencing approaches targeting different 16S rRNA variable regions may have on the human milk microbiota profiling results. This hampers our ability to make meaningful comparisons across studies. In this context, the main purpose of the present study was to re-process and re-sequence the microbiome in a large set of human milk samples (n = 412) collected from healthy women living at diverse international sites (Spain, Sweden, Peru, United States, Ethiopia, Gambia, Ghana and Kenya), by targeting a different 16S rRNA variable region and reaching a larger sequencing depth. Despite some differences between the results obtained from both sequencing approaches were notable (especially regarding alpha and beta diversities and Proteobacteria representation), results indicate that both sequencing approaches revealed a relatively consistent microbiota configurations in the studied cohorts. Our data expand upon the milk microbiota results we previously reported from the INSPIRE cohort and provide, for the first time across globally diverse populations, evidence of the impact that different DNA processing and sequencing approaches have on the microbiota profiles obtained for human milk samples. Overall, our results corroborate some similarities regarding the microbial communities previously reported for the INSPIRE cohort, but some differences were also detected. Understanding the impact of different sequencing approaches on human milk microbiota profiles is essential to enable meaningful comparisons across studies.

Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT02670278.
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http://dx.doi.org/10.3389/fcimb.2021.622550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027255PMC
July 2021

Key genetic variants associated with variation of milk oligosaccharides from diverse human populations.

Genomics 2021 Jul 6;113(4):1867-1875. Epub 2021 Apr 6.

Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, ID 83844, USA. Electronic address:

Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P < 4.23 to P < 4.5) gene with seven HMO and provide evidence of balancing selection for FUT2. Although polymorphisms in FUT3 were also associated with variation in lacto-N-fucopentaose II and difucosyllacto-N-tetrose, we found little evidence of selection on FUT3. To our knowledge, this is the first report of the use of genome-wide association analyses on HMO.
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http://dx.doi.org/10.1016/j.ygeno.2021.04.004DOI Listing
July 2021

Multipathogen Analysis of IgA and IgG Antigen Specificity for Selected Pathogens in Milk Produced by Women From Diverse Geographical Regions: The INSPIRE Study.

Front Immunol 2020 11;11:614372. Epub 2021 Feb 11.

Antigen Discovery Incorporated, Irvine, CA, United States.

Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic , spp. serovar Typhi, , and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for and diarrheagenic antigens, although sets of , , and some antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants.
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http://dx.doi.org/10.3389/fimmu.2020.614372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905217PMC
July 2021

Characterization of SARS-CoV-2 RNA, Antibodies, and Neutralizing Capacity in Milk Produced by Women with COVID-19.

mBio 2021 02 9;12(1). Epub 2021 Feb 9.

Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho, USA

Whether mother-to-infant SARS-CoV-2 transmission can occur during breastfeeding and, if so, whether the benefits of breastfeeding outweigh this risk during maternal COVID-19 illness remain important questions. Using RT-qPCR, we did not detect SARS-CoV-2 RNA in any milk sample (= 37) collected from 18 women following COVID-19 diagnosis. Although we detected evidence of viral RNA on 8 out of 70 breast skin swabs, only one was considered a conclusive positive result. In contrast, 76% of the milk samples collected from women with COVID-19 contained SARS-CoV-2-specific IgA, and 80% had SARS-CoV-2-specific IgG. In addition, 62% of the milk samples were able to neutralize SARS-CoV-2 infectivity , whereas milk samples collected prior to the COVID-19 pandemic were unable to do so. Taken together, our data do not support mother-to-infant transmission of SARS-CoV-2 via milk. Importantly, milk produced by infected mothers is a beneficial source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness. Results from prior studies assaying human milk for the presence of SARS-CoV-2, the causative virus of COVID-19, have suggested milk may act as a potential vehicle for mother-to-child transmission. Most previous studies are limited because they followed only a few participants, were cross-sectional, and/or failed to report how milk was collected and/or analyzed. As such, considerable uncertainty remains regarding whether human milk is capable of transmitting SARS-CoV-2 from mother to child. Here, we report that repeated milk samples collected from 18 women following COVID-19 diagnosis did not contain SARS-CoV-2 RNA; however, risk of transmission via breast skin should be further evaluated. Importantly, we found that milk produced by infected mothers is a source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness as milk likely provides specific immunologic benefits to infants.
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http://dx.doi.org/10.1128/mBio.03192-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885115PMC
February 2021

Evaluation of the Efficacy of a Cholera-Toxin-Based Vaccine against Bovine Intramammary Challenge.

Vaccines (Basel) 2020 Dec 24;9(1). Epub 2020 Dec 24.

Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA.

() is a primary agent of bovine mastitis and a source of significant economic loss for the dairy industry. We previously reported antigen-specific immune induction in the milk and serum of dairy cows following vaccination with a cholera toxin A and B subunit (CTA/B) based vaccine containing the iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) antigens of (IsdA + ClfA-CTA/B). The goal of the current study was to assess the efficacy of this vaccine to protect against infection after intramammary challenge. Six mid-lactation heifers were randomized to vaccinated and control groups. On days 1 and 14 animals were inoculated intranasally with vaccine or vehicle control, and on day 20 animals were challenged with . Clinical outcome, milk quality, bacterial shedding, and somatic cell count (SCC) were followed for ten days post-challenge. Vaccinated animals did not show signs of clinical mastitis and had lower SCCs compared to control animals during the challenge period. Reductions in bacterial shedding were observed but were not significant between groups. Antibody analysis of milk and serum indicated that, upon challenge, vaccinated animals produced enhanced IsdA- and ClfA-CTA/B specific immunoglobulin G (IgG) responses, while responses to CTA/B alone were not different between groups. Responses after challenge were largely IgG1 against the IsdA antigen and mixed IgG1/IgG2 against the ClfA antigen. In addition, there was a significant increase in interferon gamma (IFN-γ) expression from blood cells in vaccinated animals on day 20. While preliminary, these findings support evidence of the induction of active immunity by IsdA + ClfA-CTA/B, and further assessment of this vaccine is warranted.
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http://dx.doi.org/10.3390/vaccines9010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824273PMC
December 2020

Catheter entrapment in the Chiari network during catheter ablation.

HeartRhythm Case Rep 2020 Dec 21;6(12):896-898. Epub 2020 Aug 21.

Royal Prince Alfred Hospital, Sydney, Australia.

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http://dx.doi.org/10.1016/j.hrcr.2020.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749197PMC
December 2020

Pacing-associated cardiomyopathy in adult congenital heart disease.

Open Heart 2020 12;7(2)

Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

Objectives: Long-term single-site ventricular pacing may adversely affect ventricular function, due to dyssynchronous systemic ventricular contraction. We sought to determine the incidence, predictors and outcomes of pacing-associated cardiomyopathy (PACM) in an adult congenital heart disease (ACHD) cohort.

Methods: We retrospectively identified all patients in our database with a permanent pacemaker from 2000 to 2019. Patients were followed for the primary endpoint of unexplained decline in systemic ventricular function (PACM) and the secondary endpoint of heart failure admission.

Results: Of 2073 patients in our database, 106 had undergone pacemaker implantation. Over a median follow-up of 9.4 years, 25 patients (24%) developed PACM, but only in those with ventricular pacing percentage (VP%) ≥70%; PACM occurred in 0% of those with VP <70% and 47% of those with VP ≥70% (p<0.001). High-burden ventricular pacing (≥70%) remained predictive of PACM in transposition of the great arteries, tetralogy of Fallot and complex biventricular repair subgroups, but not in Fontan patients. Those with PACM were more likely to be admitted with heart failure (44% vs 15%, p=0.002). Cardiac resynchronisation therapy (CRT) upgrade was performed in 11 patients, with 9 responders (82%).

Conclusions: In a cohort of patients with ACHD followed long-term post-pacing, 24% developed cardiomyopathy that was significantly associated with a higher burden of ventricular pacing (VP ≥70%). Given promising response rates to CRT, patients with ACHD expected to pace in the ventricle should be closely monitored for systemic ventricular decline.
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http://dx.doi.org/10.1136/openhrt-2020-001374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768957PMC
December 2020

Mapping the Human Milk Microbiome: Impetus for a Long-Awaited Renaissance in Maternal and Infant Nutrition Research?

J Nutr 2021 02;151(2):278-280

Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, ID, USA.

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http://dx.doi.org/10.1093/jn/nxaa373DOI Listing
February 2021

COVID-19 and human milk: SARS-CoV-2, antibodies, and neutralizing capacity.

medRxiv 2020 Sep 18. Epub 2020 Sep 18.

Background: It is not known whether SARS-CoV-2 can be transmitted from mother to infant during breastfeeding, and if so whether the benefits of breastfeeding outweigh this risk. This study was designed to evaluate 1) if SARS-CoV-2 RNA can be detected in milk and on the breast of infected women, 2) concentrations of milk-borne anti-SARS-CoV-2 antibodies, and 3) the capacity of milk to neutralize SARS-CoV-2 infectivity.

Methods: We collected 37 milk samples and 70 breast swabs (before and after breast washing) from 18 women recently diagnosed with COVID-19. Samples were analyzed for SARS-CoV-2 RNA using RT-qPCR. Milk was also analyzed for IgA and IgG specific for the nucleocapsid protein, receptor binding domain (RBD), S2 subunit of the spike protein of SARS-CoV-2, as well as 2 seasonal coronaviruses using ELISA; and for its ability to neutralize SARS-CoV-2.

Results: We did not detect SARS-CoV-2 RNA in any milk sample. In contrast, SARS-CoV-2 RNA was detected on several breast swabs, although only one was considered conclusive. All milk contained SARS-CoV-2-specific IgA and IgG, and levels of anti-RBD IgA correlated with SARS-CoV-2 neutralization. Strong correlations between levels of IgA and IgG to SARS-CoV-2 and seasonal coronaviruses were noted.

Conclusions: Our data do not support maternal-to-child transmission of SARS-CoV-2 via milk; however, risk of transmission via breast skin should be further evaluated. Importantly, milk produced by infected mothers is a source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness.
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http://dx.doi.org/10.1101/2020.09.16.20196071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523143PMC
September 2020

SARS-CoV-2 and human milk: what is the evidence?

medRxiv 2020 Apr 11. Epub 2020 Apr 11.

Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, USA.

The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical, and public health communities have rapidly engaged to find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. While respiratory droplets are a known mechanism of transmission, other mechanisms are possible. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronavirus (including SARS-CoV-2) via human milk and/or breastfeeding. There is a single study providing some evidence of vertical transmission of human coronavirus 229E, a single study evaluating presence of SARS-CoV in human milk (it was negative), and no published data on MERS-CoV and human milk. There are 9 case studies of human milk tested for SARS-CoV-2; none detected the virus. Importantly, none of the published studies on coronaviruses and human milk report validation of their analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.
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http://dx.doi.org/10.1101/2020.04.07.20056812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217082PMC
April 2020

Defibrillators in adult congenital heart disease: Long-term risk of appropriate shocks, inappropriate shocks, and complications.

Pacing Clin Electrophysiol 2020 07 11;43(7):746-753. Epub 2020 Jun 11.

Sydney Medical School, The University of Sydney, Camperdown, Australia.

Aims: Sudden cardiac death (SCD) accounts for up to 25% of deaths in the adult congenital heart disease (ACHD) population. Current guidelines for defibrillator implantation are either extrapolated from acquired cardiac disease or are based upon single lesion studies, predominantly Tetralogy of Fallot (TOF). Defibrillator-related morbidity appears to be substantially higher in ACHD patients.

Methods: We retrospectively evaluated all patients in our ACHD database who received an implantable cardioverter-defibrillator (ICD) between 2000 and 2019, and who were ≥16 years old at time of implant. Patients were followed for appropriate shocks, inappropriate shocks, and complications.

Results: Of 4748 patients in our database, 59 patients (1.2%) underwent ICD implantation. ICDs were for primary prevention in 63% and secondary prevention in 37%. Over a median follow-up of 6.6 years, 24% received an appropriate shock, 27% an inappropriate shock, and 42% suffered a device-related complication (annualized risks of 3.2%, 3.6%, and 5.7%, respectively). There were no significant predictors of appropriate shocks or inappropriate shocks. All appropriate shocks in primary prevention patients occurred in TOF or transposition of the great arteries (TGA) with atrial switch, typically in the presence of multiple SCD risk factors. The majority of inappropriate shocks were due to supraventricular arrhythmias. Device-related mortality was 1.7% (0.3% per annum).

Conclusions: Appropriate shocks were relatively common in an ACHD ICD population followed in the long term. Device-related morbidity was significant. Although risk factors have been established for TOF, and to a lesser extent TGA, risk stratification for ICD implantation in ACHD remains challenging.
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http://dx.doi.org/10.1111/pace.13974DOI Listing
July 2020

SARS-CoV-2 and human milk: What is the evidence?

Matern Child Nutr 2020 10 30;16(4):e13032. Epub 2020 May 30.

Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho, USA.

The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS-CoV in human milk (it was negative); and no published data on MERS-CoV and human milk. We identified 13 studies reporting human milk tested for SARS-CoV-2; one study (a non-peer-reviewed preprint) detected the virus in one milk sample, and another study detected SARS-CoV-2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.
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http://dx.doi.org/10.1111/mcn.13032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300480PMC
October 2020

Strong Multivariate Relations Exist Among Milk, Oral, and Fecal Microbiomes in Mother-Infant Dyads During the First Six Months Postpartum.

J Nutr 2019 06;149(6):902-914

School of Family and Consumer Sciences, University of Idaho, Moscow, ID.

Background: Neonatal gastrointestinal (GI) bacterial community structure may be related to bacterial communities of the mother, including those of her milk. However, very little is known about the diversity in and relationships among complex bacterial communities in mother-infant dyads.

Objective: Our primary objective was to assess whether microbiomes of milk are associated with those of oral and fecal samples of healthy lactating women and their infants.

Methods: Samples were collected 9 times from day 2 to 6 mo postpartum from 21 healthy lactating women and their infants. Milk was collected via complete breast expression, oral samples via swabs, and fecal samples from tissue (mothers) and diapers (infants). Microbiomes were characterized using high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene. Alpha and beta diversity indices were used to compare microbiomes across time and sample types. Membership and composition of microbiomes were analyzed using nonmetric multidimensional scaling and canonical correlation analysis (CCA). The contribution of various bacterial communities of the mother-infant dyad to both milk and infant fecal bacterial communities were estimated using SourceTracker2.

Results: Bacterial community structures were relatively unique to each sample type. The most abundant genus in milk and maternal and infant oral samples was Streptococcus (47.1% ± 2.3%, 53.9% ± 1.3%, and 69.1% ± 1.8%, respectively), whereas Bacteroides were predominant in maternal and infant fecal microbiomes (22.9% ± 1.3% and 21.4% ± 2.4%, respectively). The milk microbiome was more similar to the infant oral microbiome than the infant fecal microbiome. However, CCA suggested strong associations between the complex microbial communities of milk and those of all other sample types collected.

Conclusions: These findings suggest complex microbial interactions between breastfeeding mothers and their infants and support the hypothesis that variation in the milk microbiome may influence the infant GI microbiome.
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http://dx.doi.org/10.1093/jn/nxy299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543206PMC
June 2019

What's Normal? Microbiomes in Human Milk and Infant Feces Are Related to Each Other but Vary Geographically: The INSPIRE Study.

Front Nutr 2019 17;6:45. Epub 2019 Apr 17.

Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, United States.

Microbial communities in human milk and those in feces from breastfed infants vary within and across populations. However, few researchers have conducted cross-cultural comparisons between populations, and little is known about whether certain "core" taxa occur normally within or between populations and whether variation in milk microbiome is related to variation in infant fecal microbiome. The purpose of this study was to describe microbiomes of milk produced by relatively healthy women living at diverse international sites and compare these to the fecal microbiomes of their relatively healthy infants. We analyzed milk ( = 394) and infant feces ( = 377) collected from mother/infant dyads living in 11 international sites (2 each in Ethiopia, The Gambia, and the US; 1 each in Ghana, Kenya, Peru, Spain, and Sweden). The V1-V3 region of the bacterial 16S rRNA gene was sequenced to characterize and compare microbial communities within and among cohorts. Core genera in feces were , and , and in milk were and , although substantial variability existed within and across cohorts. For instance, relative abundance of was highest in feces from rural Ethiopia and The Gambia, and lowest in feces from Peru, Spain, Sweden, and the US; was relatively more abundant in milk produced by women in rural Ethiopia than all other cohorts. Bacterial diversity also varied among cohorts. For example, Shannon diversity was higher in feces from Kenya than Ghana and US-California, and higher in rural Ethiopian than Ghana, Peru, Spain, Sweden, and US-California. There were limited associations between individual genera in milk and feces, but community-level analyses suggest strong, positive associations between the complex communities in these sample types. Our data provide additional evidence of within- and among-population differences in milk and infant fecal bacterial community membership and diversity and support for a relationship between the bacterial communities in milk and those of the recipient infant's feces. Additional research is needed to understand environmental, behavioral, and genetic factors driving this variation and association, as well as its significance for acute and chronic maternal and infant health.
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http://dx.doi.org/10.3389/fnut.2019.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479015PMC
April 2019

Household composition and the infant fecal microbiome: The INSPIRE study.

Am J Phys Anthropol 2019 07 22;169(3):526-539. Epub 2019 Apr 22.

Department of Anthropology, Washington State University, Pullman, Washington.

Objectives: Establishment and development of the infant gastrointestinal microbiome (GIM) varies cross-culturally and is thought to be influenced by factors such as gestational age, birth mode, diet, and antibiotic exposure. However, there is little data as to how the composition of infants' households may play a role, particularly from a cross-cultural perspective. Here, we examined relationships between infant fecal microbiome (IFM) diversity/composition and infants' household size, number of siblings, and number of other household members.

Materials And Methods: We analyzed 377 fecal samples from healthy, breastfeeding infants across 11 sites in eight different countries (Ethiopia, The Gambia, Ghana, Kenya, Peru, Spain, Sweden, and the United States). Fecal microbial community structure was determined by amplifying, sequencing, and classifying (to the genus level) the V1-V3 region of the bacterial 16S rRNA gene. Surveys administered to infants' mothers identified household members and composition.

Results: Our results indicated that household composition (represented by the number of cohabitating siblings and other household members) did not have a measurable impact on the bacterial diversity, evenness, or richness of the IFM. However, we observed that variation in household composition categories did correspond to differential relative abundances of specific taxa, namely: Lactobacillus, Clostridium, Enterobacter, and Klebsiella.

Discussion: This study, to our knowledge, is the largest cross-cultural study to date examining the association between household composition and the IFM. Our results indicate that the social environment of infants (represented here by the proxy of household composition) may influence the bacterial composition of the infant GIM, although the mechanism is unknown. A higher number and diversity of cohabitants and potential caregivers may facilitate social transmission of beneficial bacteria to the infant gastrointestinal tract, by way of shared environment or through direct physical and social contact between the maternal-infant dyad and other household members. These findings contribute to the discussion concerning ways by which infants are influenced by their social environments and add further dimensionality to the ongoing exploration of social transmission of gut microbiota and the "old friends" hypothesis.
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http://dx.doi.org/10.1002/ajpa.23843DOI Listing
July 2019

Pacemakers are associated with a higher risk of late death and transplantation in the Fontan population.

Int J Cardiol 2019 May 25;282:33-37. Epub 2019 Jan 25.

Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia; Murdoch Childrens Research Institute, Heart Research Group, Melbourne, VIC, Australia; Department of Cardiac Surgery, Royal Children's Hospital, Melbourne, VIC, Australia. Electronic address:

Background: The need for permanent pacing has been identified as a predictor of poor outcomes in the late survivors of Fontan surgery. However, it is not clear if the need for a pacemaker is a surrogate marker of a declining Fontan state, or if pacing is deleterious to the Fontan circulation.

Objectives: We sought to compare the long-term outcomes of propensity-matched Fontan patients with and without a permanent pacemaker.

Methods: Patients who have survived Fontan completion with a documented history of cardiac arrhythmia were identified from the Australia and New Zealand Fontan Registry. Pacemaker insertion details, cardiac function and electrophysiological data were obtained for the patients with a permanent pacemaker. Survival analysis was performed with propensity score matching to compare late survival and outcomes in patients with versus without a pacemaker.

Results: There was a total of 310 patients with a history of cardiac arrhythmia, of which 126 (41%) had a permanent pacemaker. After propensity-score matching, 99 pairs were generated (n = 198). Patients with a permanent pacemaker had a higher risk of death (HR 3.32 95% CI 1.60-6.90, p = 0.001) and death or transplantation (HR 3.55 95% CI 1.87-6.73, p < 0.001). Patients who were only paced atrially were not at a significantly increased risk of death or transplantation. However, patients who were ventricular paced >50% of the time were much more likely to encounter late death or transplantation (HR 3.82 95% CI 1.64-8.95, p = 0.002).

Conclusions: Having a permanent pacemaker and needing ventricular pacing is likely associated with an increased risk of death and transplantation in patients with a Fontan circulation.
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http://dx.doi.org/10.1016/j.ijcard.2019.01.088DOI Listing
May 2019

Ablation of Atrial Arrhythmias After the Atriopulmonary Fontan Procedure: Mechanisms of Arrhythmia and Outcomes.

JACC Clin Electrophysiol 2018 10;4(10):1338-1346

Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; Sydney Medical School, The University of Sydney, Camperdown, New South Wales, Australia. Electronic address:

Objectives: This study sought to describe atrial arrhythmia mechanisms, acute outcomes, and long-term arrhythmia burdens following catheter ablation in adult atriopulmonary (AP) Fontan patients.

Background: Atrial arrhythmias are a significant cause of morbidity and mortality in the AP Fontan population.

Methods: Sixty consecutive atrial arrhythmia ablations were reviewed in 42 AP Fontan patients (31 ± 8 years of age), performed between 1998 and 2017. The number of induced and ablated tachycardias was recorded for each case, as well as the ability to ablate the suspected clinical tachycardia. Longer-term arrhythmia burden was assessed by using a 12-point clinical arrhythmia severity score.

Results: Intra-atrial re-entrant tachycardia (IART) was induced in 93% of cases (n = 56), atrioventricular re-entrant tachycardia in 2 (3%) and atrioventricular nodal re-entrant tachycardia in a single case. The mean number of tachycardias induced per case was 2.3. The critical isthmus for IART was mapped to the lateral (n = 10), inferolateral (n = 8), posterior/posterolateral (n = 16), or septal (n = 10) systemic venous atrium, or to the pulmonary venous atrium (n = 4). Ablation of all inducible tachycardias was achieved in 62%, ablation of at least one (but not all) inducible tachycardias in 25%, with failure to ablate any tachycardias in 13%. The suspected clinical arrhythmia was ablated in 50 cases (83%). Catheter ablation resulted in a significant reduction in arrhythmia score at 3 to 6, 12, and 24 months, irrespective of whether all inducible tachycardias were ablated, or the suspected clinical arrhythmia only. Twelve patients (29%) underwent at least one repeat ablation procedure, with a mean time between ablations of 2.7 ± 3.0 years. There were no cases of periprocedural death, stroke or cardiac tamponade.

Conclusions: Catheter ablation can be a safe and effective intervention that will significantly reduce arrhythmia burden in the AP Fontan patient.
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http://dx.doi.org/10.1016/j.jacep.2018.08.012DOI Listing
October 2018

Adverse effects of amiodarone therapy in adults with congenital heart disease.

Congenit Heart Dis 2018 Nov 21;13(6):944-951. Epub 2018 Sep 21.

Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Objective: Amiodarone is a highly effective antiarrhythmic therapy, however its toxicity profile often limits treatment. This is particularly relevant in adults with congenital heart disease (CHD), who are often young and in whom other antiarrhythmic agents commonly fail or are contraindicated. We sought to determine incidence and predictors of adverse effects caused by amiodarone in adult CHD (ACHD).

Design: A retrospective review of patients with moderate to complex ACHD treated with amiodarone at our center between 2000 and 2017 was performed. Incidence and predictors of adverse effects were described. Efficacy of amiodarone therapy in controlling the clinical arrhythmia was assessed as complete, partial, or failed.

Results: Amiodarone was prescribed in 57 patients of 902 ACHD patients reviewed (6%), for a mean duration of 2.7 ± 4.3 years. Significant adverse effects occurred in 56%, most commonly thyroid dysfunction, with amiodarone-induced thyrotoxicosis (AIT) in 30% and amiodarone-induced hypothyroidism in 14%. AIT frequently led to arrhythmia exacerbation and occurred most in those with Fontan anatomy. Severe dermatological effects were seen in 7% and bradycardia requiring pacing in 5%. Interstitial lung disease, peripheral neuropathy and alopecia were observed in single cases. Amiodarone toxicity led to discontinuation of the drug in 42%. Amiodarone was highly effective when tolerated, however, achieving complete arrhythmia control in 63%, partial control in 35%, with failure to control in only one patient.

Conclusions: Amiodarone therapy is effective in moderate to complex ACHD patients, but is frequently limited by adverse effects. ACHD patients seem especially vulnerable to thyroid dysfunction, with Fontan patients in particular at increased risk of AIT.
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http://dx.doi.org/10.1111/chd.12657DOI Listing
November 2018

Efficacy and adverse effects of sotalol in adults with congenital heart disease.

Int J Cardiol 2019 Jan 20;274:74-79. Epub 2018 Jun 20.

University of Sydney Medical School and Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia. Electronic address:

Introduction: Adults with congenital heart disease (CHD) are predisposed to arrhythmias, which can often be refractory to medical therapy. Sotalol is an attractive alternative antiarrhythmic to amiodarone in this younger patient population, given the latter's toxicity profile, but it may have proarrhythmic effects. We therefore aimed to assess the efficacy and safety of sotalol in adults with CHD.

Methods: We retrospectively assessed our adult CHD database for all patients ≥16 years old, with moderate to highly complex defects, who were prescribed sotalol between 2000 and 2017. Efficacy in treating the clinical arrhythmia was assessed as complete, partial or failure. Adverse effects, including proarrhythmia, were documented.

Results: Sotalol was prescribed in 82 of 902 adult CHD patients reviewed (9%). The mean age at sotalol commencement was 31.8 ± 13.1 years, with a median time on sotalol of 2.8 years. The average prescribed dose was 122 ± 51 mg/daily. Sotalol was completely effective in 48% (n = 39), partially effective in 46% (n = 38) and failed to control the clinical arrhythmia in 6% (n = 5). Fifteen patients (18%) discontinued sotalol due to a side effect, most commonly fatigue or dyspnoea. No episodes of torsades de pointes or sudden cardiac death were observed. Significant bradycardia related to sotalol occurred in 13% (n = 11, with permanent pacing implemented in 4), and was associated with Fontan anatomy.

Conclusions: In moderate to highly complex adult CHD, sotalol was reasonably effective and safe in low doses. Side effects limiting treatment were typically non-life-threatening, with significant bradycardia related to sotalol more likely in Fontan patients.
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http://dx.doi.org/10.1016/j.ijcard.2018.06.066DOI Listing
January 2019

Broad complex tachycardia in a patient with a pacemaker: What is the mechanism?

HeartRhythm Case Rep 2018 Jun 20;4(6):232-236. Epub 2018 Mar 20.

Prince of Wales Hospital and Eastern Heart Clinic, Randwick, Australia.

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http://dx.doi.org/10.1016/j.hrcr.2018.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006419PMC
June 2018

Social networks, cooperative breeding, and the human milk microbiome.

Am J Hum Biol 2018 07 26;30(4):e23131. Epub 2018 Apr 26.

School of Biological Sciences, Washington State University, Pullman, Washington.

Objectives: We present the first available data on the human milk microbiome (HMM) from small-scale societies (hunter-gatherers and horticulturalists in the Central African Republic [CAR]) and explore relationships among subsistence type and seasonality on HMM diversity and composition. Additionally, as humans are cooperative breeders and, throughout our evolutionary history and today, we rear offspring within social networks, we examine associations between the social environment and the HMM. Childrearing and breastfeeding exist in a biosocial nexus, which we hypothesize influences the HMM.

Methods: Milk samples from hunter-gatherer and horticultural mothers (n = 41) collected over two seasons, were analyzed for their microbial composition. A subsample of these women's infants (n = 33) also participated in detailed naturalistic behavioral observations which identified the breadth of infants' social and caregiving networks and the frequency of contact they had with caregivers.

Results: Analyses of milk produced by CAR women indicated that HMM diversity and community composition were related to the size of the mother-infant dyad's social network and frequency of care that infants receive. The abundance of some microbial taxa also varied significantly across populations and seasons. Alpha diversity, however, was not related to subsistence type or seasonality.

Conclusion: While the origins of the HMM are not fully understood, our results provide evidence regarding possible feedback loops among the infant, the mother, and the mother's social network that might influence HMM composition.
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http://dx.doi.org/10.1002/ajhb.23131DOI Listing
July 2018

Atrial flow dynamics as a determinant of tissue temperature during balloon cryoablation.

Europace 2018 11;20(FI_3):f451-f457

The Royal Prince Alfred Hospital and University of Sydney, Missenden Road, Camperdown, Sydney, Australia.

Aims: Balloon cryoablation is an accepted method of achieving pulmonary vein isolation for the treatment of atrial fibrillation. The relationship between blood flow in the atrium and cryo energy delivery to the tissue remains poorly understood.

Methods And Results: Controlled cryoablations were performed in vitro using a pulmonary vein phantom constructed from bovine muscle, providing a 20 mm vein ostium. A temperature sensor was mounted within the 'vein wall' at a 1 mm tissue depth. Apparatus was constructed to assess the effect of incomplete pulmonary venous occlusion causing a leak, simulated atrial stasis, atrial circulation, and mitral regurgitation. Controlled ablations using the 2nd generation 28 mm cryoballoon catheter were repeated three times and mean values compared. Leak volume significantly affected both balloon temperatures and tissue temperatures. Simulated mitral regurgitation (MR) significantly impaired the effectiveness of cryo energy delivery resulting in significantly warmer balloon and tissue temperatures. With high leak volumes and moderate to severe MR there was a marked disparity between the cryoballoon temperature and the tissue temperature of approximately 60 degrees. Balloon warming times varied inversely with both leak volume and simulated MR flow volume.

Conclusion: Incomplete venous occlusion and MR result in warmer balloon and tissue temperatures, and shorter balloon warming times, and are likely to significantly impair the effectiveness of cryoablation. Balloon temperature is poor indicator of tissue temperature under higher flow conditions.
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http://dx.doi.org/10.1093/europace/eux190DOI Listing
November 2018

Comparison of commercially-available preservatives for maintaining the integrity of bacterial DNA in human milk.

J Microbiol Methods 2017 10 9;141:73-81. Epub 2017 Aug 9.

School of Biological Sciences, Washington State University, Pullman, WA, United States; Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA, United States. Electronic address:

Background: Inhibiting changes to bacteria in human milk between sample collection and analysis is necessary for unbiased characterization of the milk microbiome. Although cold storage is considered optimal, alternative preservation is sometimes necessary.

Research Aim/question: The objective of this study was to compare the effectiveness of several commercially-available preservatives with regard to maintaining bacterial DNA in human milk for delayed microbiome analysis. Specifically, we compared Life Technologies' RNAlater® stabilization solution, Biomatrica's DNAgard® Saliva, Advanced Instruments' Broad Spectrum Microtabs II™, and Norgen Biotek Corporation's Milk DNA Preservation and Isolation Kit.

Methods: Aliquots of 8 pools of human milk were treated with each preservative. DNA was extracted immediately and at 1, 2, 4, and 6wk, during which time milk was held at 37°C. The V1-V3 region of the bacterial 16S rRNA gene was amplified and sequenced. Changes in bacterial community structure and diversity over time were evaluated.

Results: Comparable to other studies, the most abundant genera were Streptococcus (33.3%), Staphylococcus (14.0%), Dyella (6.3%), Pseudomonas (3.0%), Veillonella (2.5%), Hafnia (2.0%), Prevotella (1.7%), Rhodococcus (1.6%), and Granulicatella (1.4%). Overall, use of Norgen's Milk DNA Preservation and Isolation Kit best maintained the consistency of the bacterial community structure. Total DNA, diversity, and evenness metrics were also highest in samples preserved with this method.

Conclusions: When collecting human milk for bacterial community analysis in field conditions where cold storage is not available, our results suggest that Norgen's Milk DNA Preservation and Isolation Kit may be a useful method, at least for a period of 2weeks.
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http://dx.doi.org/10.1016/j.mimet.2017.08.002DOI Listing
October 2017

Human Milk Microbial Community Structure Is Relatively Stable and Related to Variations in Macronutrient and Micronutrient Intakes in Healthy Lactating Women.

J Nutr 2017 09 19;147(9):1739-1748. Epub 2017 Jul 19.

School of Biological Sciences and

The human milk microbiome has been somewhat characterized, but little is known about changes over time and relations with maternal factors such as nutrient intake. We sought to characterize the human milk microbiome and described associations with maternal nutrient intake, time postpartum, delivery mode, and body mass index (BMI; in kg/m). Milk samples ( = 104) and 24-h diet recalls were collected 9 times from 21 healthy lactating women from day 2 to 6 mo postpartum. Women were classified by BMI as healthy weight (<25) or overweight or obese (≥25). Bacterial taxa were characterized with the use of the high-throughput sequencing of the 16S ribosomal RNA gene. The milk microbiome was relatively constant over time, although there were small changes in some of the lesser-abundant genera. Relative abundances of several taxa were associated with BMI, delivery mode, and infant sex. For instance, overweight and obese mothers produced milk with a higher relative abundance of than did healthy-weight women (1.8% ± 0.6% compared with 0.4% ± 0.2%, respectively; < 0.05). Relative abundances of several bacterial taxa were also associated with variations in maternal dietary intake. For example, intakes of saturated fatty acids ( = -0.59; = 0.005) and monounsaturated fatty acids ( = -0.46; = 0.036) were inversely associated with the relative abundance of ; total carbohydrates ( = -0.54; = 0.011), disaccharides ( = -0.47; = 0.031), and lactose ( = -0.51; = 0.018) were negatively associated with Firmicutes; and protein consumption was positively correlated with the relative abundance of ( = 0.46; = 0.037). Factors associated with variations in the human milk microbiome are complex and may include maternal nutrient intake, maternal BMI, delivery mode, and infant sex. Future studies designed to investigate the relation between maternal nutrient intake and the milk microbiome should strive to also evaluate dietary supplement usage and analyze the collected milk for its nutrient content.
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http://dx.doi.org/10.3945/jn.117.248864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572491PMC
September 2017
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