Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jul 11:2:24.
doi: 10.1186/2049-2618-2-24. eCollection 2014.

Effect of chemotherapy on the microbiota and metabolome of human milk, a case report

Camilla Urbaniak  1 , Amy McMillan  1 , Michelle Angelini  2 , Gregory B Gloor  3 , Mark Sumarah  4 , Jeremy P Burton  1 , Gregor Reid  1
Affiliations

Effect of chemotherapy on the microbiota and metabolome of human milk, a case report

Camilla Urbaniak et al. Microbiome. .

Abstract

Background: Human milk is an important source of bacteria for the developing infant and has been shown to influence the bacterial composition of the neonatal gut, which in turn can affect disease risk later in life. Human milk is also an important source of nutrients, influencing bacterial composition but also directly affecting the host. While recent studies have emphasized the adverse effects of antibiotic therapy on the infant microbiota, the effects of maternal chemotherapy have not been previously studied. Here we report the effects of drug administration on the microbiota and metabolome of human milk.

Methods: Mature milk was collected every two weeks over a four month period from a lactating woman undergoing chemotherapy for Hodgkin's lymphoma. Mature milk was also collected from healthy lactating women for comparison. Microbial profiles were analyzed by 16S sequencing and the metabolome by gas chromatography-mass spectrometry.

Findings: Chemotherapy caused a significant deviation from a healthy microbial and metabolomic profile, with depletion of genera Bifidobacterium, Eubacterium, Staphylococcus and Cloacibacterium in favor of Acinetobacter, Xanthomonadaceae and Stenotrophomonas. The metabolites docosahexaenoic acid and inositol known for their beneficial effects were also decreased.

Conclusion: With milk contents being critical for shaping infant immunity and development, consideration needs to be given to the impact of drugs administered to the mother and the long-term potential consequences for the health of the infant.

Keywords: 16S rRNA gene sequencing; Human milk microbiome; Metabolome.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Summary of clinical data and sample collection. Milk samples were collected from a lactating woman undergoing chemotherapy for Hodgkin’s lymphoma. Milk samples were collected every 2 weeks over a 4-month period. At each session milk was collected 15 to 30 minutes before (sample A) and after (sample B) chemotherapy. The duration of chemotherapy treatment was 2 hours. No milk was collected at week 8 due to scheduling conflicts.
Figure 2
Figure 2
Changes in bacterial diversity as a result of chemotherapy. Bacterial diversity within a sample (i.e. alpha diversity) was measured by calculating Shannon’s diversity index. Each point on the graph represents a subject with the line representing the mean for all samples within a group. The higher the index the greater the bacterial diversity found within a sample. The mean of the ‘Wk0/H’ group (week 0 and healthy samples) was 4.3, and that of the chemotherapy group (weeks 2 to 16) was 2.8. Groups were statistically different from each other as measured by unpaired Student’s t-test (P < 0.05).
Figure 3
Figure 3
16S rRNA sequencing analysis of bacteria in human milk. Milk samples were collected from a lactating woman undergoing chemotherapy as described in Figure 1 as well as from eight healthy lactating women. (A) Weighted UniFrac PCoA plot. Each milk sample, represented by a coloured circle, is plotted on this three-dimensional, three-axis plane representing 84% of the variation observed between all samples. Samples that cluster together are similar in biota composition and abundance. Orange circles represent samples collected from weeks 4 to 16 of chemotherapy, blue circles represent samples collected at week 2 of chemotherapy, purple circles represent samples collected at week 0, red circles represent milk samples from healthy lactating women (only one time point) and green circles represent milk samples from a healthy lactating women collected 4-months apart. As shown by the plot, there were three distinct groups: (i) week 0 samples and healthy milk samples; (ii) week 2 of chemotherapy; and (iii) weeks 4 to 16 of chemotherapy. Data were rarified to 735 reads/sample. (B) Barplot showing the relative abundances of different genera in each sample. Each bar represents a subject and each coloured box a different genus. The height of the coloured boxes represents the relative abundance of that genus within the sample. Genera that were less than 2% abundant in a given sample were placed in the ‘Remaining fraction’ at the top of the graph (grey boxes).
Figure 4
Figure 4
Comparison of relative proportions of bacterial taxa between treatments. Boxplots comparing six bacterial taxa between samples collected during chemotherapy (weeks 4 to 16) and those without treatment (week 0 and healthy samples (Wk0/H)). The box signifies the 75% (upper) and 25% (lower) quartiles and thus shows where 50% of the samples lie. The black line inside the box represents the median. The whiskers represent the lowest datum still within 1.5 interquartile range (IQR) of the lower quartile and the highest datum still within 1.5 IQR of the upper quartile. Outliers are shown with open circles. The value ‘0’ represents the geometric mean abundance; thus, values above 0 are more abundant and values less than 0 are less abundant than the geometric mean. Significant differences were observed between the two groups for all taxa graphed (Mann-Whitney U test P < 0.05, FDR <0.1).
Figure 5
Figure 5
Principle component analysis of metabolites in breast milk at week 0 and during chemotherapy. (A) Scoreplot displaying the distribution of samples based on metabolites alone, where the distance between samples represents how similar the metabolome of those samples are. Each point represents the average of two technical replicates. (B) Loadings plot. Each point represents a metabolite. Metabolites present in a given quadrant of the loadings plot are present in highest abundance in samples present in the same quadrant of the scoreplot (A).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Martin V, Maldonado-Barragan A, Moles L, Rodriguez-Banos M, Campo RD, Fernandez L, Rodriguez JM, Jimenez E. Sharing of bacterial strains between breast milk and infant feces. J Hum Lact. 2012;28:36–44. - PubMed
    1. Martin R, Langa S, Reviriego C, Jiminez E, Marin ML, Xaus J, Fernandez L, Rodriguez JM. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr. 2003;143:754–758. - PubMed
    1. Stuebe A. The risks of not breastfeeding for mothers and infants. Rev Obstet Gynecol. 2009;2:222–231. - PMC - PubMed
    1. Silvers KM, Frampton CM, Wickens K, Pattemore PK, Ingham T, Fishwick D, Crane J, Town GI, Epton MJ. New Zealand Asthma and Allergy Cohort Study Group. Breastfeeding protects against current asthma up to 6 years of age. J Pediatr. 2012;160:991–6.e1. - PubMed
    1. Guaraldi F, Salvatori G. Effect of breast and formula feeding on gut microbiota shaping in newborns. Front Cell Infect Microbiol. 2012;2:94. - PMC - PubMed

LinkOut - more resources