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

Urbaniak C, McMillan A, Angelini M, Gloor GB, Sumarah M, Burton JP, Reid G - Microbiome (2014)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lawson Health Research Institute, 268 Grosvenor Street, London, ON N6A 4V2, Canada ; Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada.

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.

No MeSH data available.


Related in: MedlinePlus

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4109383&req=5

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).

Mentions: Chemotherapy affected both bacterial diversity and bacterial profiles in human milk. Bacterial diversity within samples was lower in milk collected throughout chemotherapy compared with milk samples collected at week 0 and from healthy lactating women (Figure 2). Bacterial profiles at week 0 were similar to those from healthy women, although this changed within 2 weeks of treatment (Figure 3A). Samples collected at weeks 4 to 16 shared similar profiles and differed from week 2 and from week 0/healthy samples (Figure 3A). These differences were not due to natural changes over time, as the bacterial community in two milk samples analyzed from a healthy subject did not change over a 4-month period (Figure 3A, green samples). The bar plot in Figure 3B shows the bacterial communities present in these samples with a striking increase in abundances of Acinetobacter and Xanthomonadaceae in milk collected during chemotherapy. A comparison of relative abundances of Acinetobacter, Xanthomonadaceae and Stenotrophomonas (a genus belonging to the Xanthomonadaceae family) between the chemotherapy (weeks 4 to 16) and non-treatment (week 0 and healthy samples) groups is displayed in Figure 4 and were significantly higher during chemotherapy. We also examined the differences between three bacteria believed to confer beneficial health effects to the infant, Bifidobacterium, Eubacterium and Lactobacillus. The first two were significantly decreased during chemotherapy whereas no differences were observed for Lactobacillus (Figure 4). Overall, a total of 22 out of the 49 genera identified were differentially abundant between the two groups (Additional file 3). While the core microbiome (that is, taxa that were present in 100% of the samples) was somewhat similar between the two groups, it is interesting to note that Stenotrophomonas was present in every chemotherapy sample and Lactobacillus and Eubacterium were present in every healthy and week 0 sample (Additional file 4).


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

Urbaniak C, McMillan A, Angelini M, Gloor GB, Sumarah M, Burton JP, Reid G - Microbiome (2014)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4109383&req=5

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).
Mentions: Chemotherapy affected both bacterial diversity and bacterial profiles in human milk. Bacterial diversity within samples was lower in milk collected throughout chemotherapy compared with milk samples collected at week 0 and from healthy lactating women (Figure 2). Bacterial profiles at week 0 were similar to those from healthy women, although this changed within 2 weeks of treatment (Figure 3A). Samples collected at weeks 4 to 16 shared similar profiles and differed from week 2 and from week 0/healthy samples (Figure 3A). These differences were not due to natural changes over time, as the bacterial community in two milk samples analyzed from a healthy subject did not change over a 4-month period (Figure 3A, green samples). The bar plot in Figure 3B shows the bacterial communities present in these samples with a striking increase in abundances of Acinetobacter and Xanthomonadaceae in milk collected during chemotherapy. A comparison of relative abundances of Acinetobacter, Xanthomonadaceae and Stenotrophomonas (a genus belonging to the Xanthomonadaceae family) between the chemotherapy (weeks 4 to 16) and non-treatment (week 0 and healthy samples) groups is displayed in Figure 4 and were significantly higher during chemotherapy. We also examined the differences between three bacteria believed to confer beneficial health effects to the infant, Bifidobacterium, Eubacterium and Lactobacillus. The first two were significantly decreased during chemotherapy whereas no differences were observed for Lactobacillus (Figure 4). Overall, a total of 22 out of the 49 genera identified were differentially abundant between the two groups (Additional file 3). While the core microbiome (that is, taxa that were present in 100% of the samples) was somewhat similar between the two groups, it is interesting to note that Stenotrophomonas was present in every chemotherapy sample and Lactobacillus and Eubacterium were present in every healthy and week 0 sample (Additional file 4).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lawson Health Research Institute, 268 Grosvenor Street, London, ON N6A 4V2, Canada ; Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada.

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.

No MeSH data available.


Related in: MedlinePlus