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Clinical Trial
. 2019 Dec 11:10:2866.
doi: 10.3389/fimmu.2019.02866. eCollection 2019.

Clostridioides difficile Colonization Is Differentially Associated With Gut Microbiome Profiles by Infant Feeding Modality at 3-4 Months of Age

Kelsea M Drall  1 , Hein M Tun  1 , Nadia P Morales-Lizcano  2 , Theodore B Konya  3 , David S Guttman  2   4 , Catherine J Field  5 , Rupasri Mandal  6 , David S Wishart  6 , Allan B Becker  7 , Meghan B Azad  7 , Diana L Lefebvre  8 , Piush J Mandhane  1 , Theo J Moraes  9 , Malcolm R Sears  8 , Stuart E Turvey  10 , Padmaja Subbarao  8   9 , James A Scott  2 , Anita L Kozyrskyj  1
Affiliations
Clinical Trial

Clostridioides difficile Colonization Is Differentially Associated With Gut Microbiome Profiles by Infant Feeding Modality at 3-4 Months of Age

Kelsea M Drall et al. Front Immunol. .

Abstract

Colonization with Clostridioides difficile occurs in up to half of infants under the age of 3 months, is strongly influenced by feeding modality and is largely asymptomatic. In spite of this, C. difficile's presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting or benefiting from changes in infant gut microbiome development, including colonization with pathogenic bacteria and disrupted production of microbial bioactive metabolites and proteins. In this study, the microbiomes of 1554 infants from the CHILD Cohort Study were described according to C. difficile colonization status and feeding mode at 3-4 months of age. C. difficile colonization was associated with a different gut microbiome profile in exclusively breastfed (EBF) vs. exclusively formula fed (EFF) infants. EBF infants colonized with C. difficile had an increased relative abundance of Firmicutes and Proteobacteria, decreased relative abundance of Bifidobacteriaceae, greater microbiota alpha-diversity, greater detectable fecal short chain fatty acids (SCFA), and lower detectable fecal secretory Immunoglobulin A (sIgA) than those not colonized. Similar but less pronounced differences were seen among partially breastfed infants (PBF) but EFF infants did not possess these differences in the gut microbiome according to colonization status. Thus, breastfed infants colonized with C. difficile appear to possess a gut microbiome that differs from non-colonized infants and resembles that of EFF infants, but the driving force and direction of this association remains unknown. Understanding these compositional differences as drivers of C. difficile colonization may be important to ensure future childhood health.

Keywords: Clostridioides difficile; SCFA; gut microbiota; infant feeding; metabolites; microbiome; sIgA.

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Figures

Figure 1
Figure 1
Frequency of C. difficile colonization in our study population and infant microbial alpha-diversity according feeding mode (n = 1,554). Colonization rates differ within feeding groups (A) 22.63% of exclusively breastfed infants (N = 193/853), 35.96% of partially breastfed infants (N = 155/431) and 49.63% of formula fed infants were colonized (N = 134/270) (Fishers' exact p < 0.001). Scatter box-plots of the median (middle line), Q3 and Q1 quartiles (box limits), IQR (whiskers) and outlying values (dots). Data were normally distributed (Supplementary Figure 3) and thus two-sided p-values were calculated with students t-test within infant feeding groups, comparing colonized and non-colonized infants at a significance threshold of α = 0.05. Higher α-diversity was observed for infants colonized with C. difficile (CD+) and breastfed (either exclusively or partially) than non-carriers (CD–) on the same diet. This was the case for both the Shannon diversity index (B) and Chao1 species richness index (C). Purple represents EBF, green for PBF and gray for EFF.
Figure 2
Figure 2
Relative differences in microbiota composition between C. difficile carriers and non-carriers across infant feeding groups (n = 1,554). Multivariate linear regression results (MaAslin) for family (bolded) and genus level taxa that are differentially associated with C. difficile colonization at 3–4 months of age. Values on the x-axis represent arcsine square root transformed regression coefficients of microbiota relative abundances for each linear model, adjusted for multiple comparisons (FDR correction) to determine which taxa are uniquely associated with C. difficile colonization. Each model had a reference of infants without C. difficile colonization at 3–4 months. Data shown only for taxa with FDR corrected two-sided q-value < 0.05. Coefficients > 0 (positive values) represent taxa that enriched in C. difficile carriers, while coefficients < 0 (negative values) represent taxa that were depleted in C. difficile carriers. P-values for each regression can be found in Supplementary Tables 3–5. Purple represents EBF (N = 853, 193 CD+), green for PBF (N = 431, 155 CD+) and gray for EFF (N = 270, 134 CD+).
Figure 3
Figure 3
Log transformed measures of fecal secretory IgA, according to infant colonization and feeding mode (n = 731). Scatter box-plots of the median (middle line), Q3 and Q1 quartiles (box limits), IQR (whiskers) and outlying values (dots). Two-sided p-values were calculated with Mann–Whitney U-test of log transformed fecal sIgA (mg/g) comparing colonized and non-colonized infants within the same diet group. Exclusively breastfed infants colonized with C. difficile (CD+) had lower median fecal sIgA than non-carriers (CD–) on the same diet. Purple represents EBF (N = 290, 72 CD+), green for PBF (N = 237, 104 CD+) and gray for EFF (N = 204, 101 CD+).
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References

    1. Jangi S, Lamont JT. Asymptomatic colonization by Clostridium difficile in infants : implications for disease in later life. J Pediatr Gastroenterol Nutr. (2010) 51:2–7. 10.1097/MPG.0b013e3181d29767 - DOI - PubMed
    1. Crobach MJT, Vernon JJ, Loo VG, Kong LY, Péchiné S, Wilcox MH, et al. . Understanding Clostridium difficile colonization. Clin Microbiol Rev. (2018) 31: e00021–17. 10.1128/CMR.00021-17 - DOI - PMC - PubMed
    1. Tsutaoka B, Hansen J, Johnson D, Holodniy M. Antibiotic-associated pseudomembranous enteritis due to Clostridium difficile. Clin Infect Dis. (1994) 18:982–94. 10.1093/clinids/18.6.982 - DOI - PubMed
    1. Penders J, Thijs C, van den Brandt PA, Kummeling I, Snijders B, Stelma F, et al. . Gut microbiota composition and development of atopic manifestations in infancy: the KOALA birth cohort study. Gut. (2007) 56:661–7. 10.1136/gut.2006.100164 - DOI - PMC - PubMed
    1. van Nimwegen FA, Penders J, Stobberingh EE, Postma DS, Koppelman GH, Kerkhof M, et al. . Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. J Allergy Clin Immunol. (2011) 128:948–55.e3. 10.1016/j.jaci.2011.07.027 - DOI - PubMed