Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria

Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria Yuki Kuriyama , Natsuki Suganuma , View ORCID Profile Kohei Ito doi: https://doi.org/10.1101/2024.12.19.629351 Yuki Kuriyama 1 BIOTA Inc. , Tokyo, 113-8510, Japan 2 Department of Biological Sciences, Graduate School of Science, The University of Tokyo , Tokyo 113-0033, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Natsuki Suganuma 3 bacterico corp. , Osaka, 530-0027, Japan 4 Division of Pharmaceutics, Faculty of Pharmacy, Keio University , Minato-ku, Tokyo, 105-8512, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kohei Ito 1 BIOTA Inc. , Tokyo, 113-8510, Japan Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kohei Ito For correspondence: kohei{at}biota.ne.jp Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Background The gut microbiome plays a crucial role in human health, and it is known that the microbiome is transmitted from mother to infant at birth and has profound effects on an individual’s health. Although extensive research has been conducted on mother-to-infant microbiome transmission, little is known about plasmid transmission and its effects on the infant microbiome. Plasmids are considered important contributors to early development of the gut microbiome due to their functions, such as antibiotic resistance, and their ability to be transferred between a wide range of host bacteria. Methods In this study, we assembled plasmid sequences from longitudinal fecal data of 65 mother-infant pairs and analyzed plasmid sharing between mothers and infants during the first year of life. After identifying shared plasmids, we investigated the relationship between plasmid sharing and delivery mode. We also characterized the functions and host range of shared plasmids. Results We found that the number of plasmids was lower in infants than in mothers, probably reflecting the lower overall diversity of the infant microbiome. Additionally, we detected shared plasmids between mothers and infants, marking the first discovery of mother-to-infant plasmid transmission. Our findings revealed that plasmids are more likely to be transmitted from mother to infant immediately after birth, with the likelihood of transmission decreasing as infants age. This underscores the critical role of the maternal microbiome in shaping early development of the gut microbiome. Moreover, plasmids from dominant bacteria in mother-to-infant microbiome transmission, such as Bacteroides , were frequently transmitted to infants and carried specific functional traits. In particular, plasmid genes such as mbpA, mbpB, and mbpC were frequently shared between mothers and infants. Each of these genes encodes a protein of a specific size and plays an important role in plasmid mobilization, or the transfer of plasmids to other bacteria. Plasmids improve the fitness and environmental adaptability of host bacteria, which may contribute to the development of a healthy gut microbiome in infants. Conclusions This study revealed that mother-to-infant plasmid transmission likely occurs during the early postpartum period and is influenced by dominant gut bacteria. These findings provide new insights into the mother’s role in shaping the infant’s gut microbiome development. Introduction The human gut microbiome plays a fundamental role in health, influencing various physiological processes, including metabolism, immune function, and the development of metabolic disorders such as obesity and diabetes [ 1 ]. The initial establishment of this microbiome occurs primarily through vertical transmission from mother to infant during birth, with profound implications for long-term health outcomes [ 2 ]. Recent investigations have highlighted the significance of plasmids in gut microbiome transmission of the gut microbiome. Plasmids are extrachromosomal DNA elements that replicate autonomously within bacteria and frequently carry genes conferring adaptive advantages, including antimicrobial resistance, toxin production, and metal tolerance. These genetic elements facilitate rapid bacterial adaptation to environmental stressors through horizontal gene transfer, which occurs via conjugation, transformation, and transduction. Conjugation, particularly prevalent in gram-negative bacteria, enables the direct transfer of plasmids to other bacteria through cell contact, substantially influencing gut microbiome diversity and functionality [ 3 ]. This horizontal gene transfer mainly occurs during parturition as the neonate traverses the birth canal and continues through early infancy via breast milk consumption and environmental exposures [ 4 ]. The role of plasmid-mediated genetic exchange appears to be important in the transmission of the gut microbiome from mother to infant. These maternal gut bacteria transmitted during birth may colonize the infant’s gut and subsequently influence microbiome development through plasmid-mediated horizontal gene transfer [ 5 – 8 ]. Of particular concern is the transfer of antibiotic resistance genes or pathogenic factors via plasmids, which could potentially impact infant health outcomes. However, the specifics of this process, particularly regarding the identity and distribution of shared plasmids between mother and infant, remain poorly understood. Delivery mode is a major factor influencing the initial colonization pattern of such gut microbiomes and plasmid transmission [ 4 ]. Vaginal delivery exposes the infant directly to the mother’s vaginal and intestinal bacteria. [ 4 , 9 ]. This exposure allows these bacteria to be pioneer colonizers of the infant’s gut microbiome. The maternal-derived microorganisms also create conditions that facilitate plasmid-mediated gene exchange in the infant’s intestinal environment. This process allows for transferring adaptive genetic elements important for immune system development and pathogen resistance, such as antibiotic-resistance genes and factors that increase microbial diversity [ 10 ]. In contrast, cesarean section bypasses this critical exposure and limits the transfer of maternal gut bacteria to the infant [ 9 ]. Instead, the gut microbiome of cesarean-delivered infants is predominantly shaped by environmental microbes, which may alter the dynamics of plasmid transfer. This shift may contribute to differences in microbiome diversity and functionality, with potential long-term health implications [ 11 ]. This study focuses on plasmid transmission from mother to infant and aims to identify three key aspects: the occurrence of plasmid sharing between mothers and infants, the difference in plasmid sharing by delivery mode, and the taxonomy and functional characteristics of shared plasmids. The results will provide an important basis for elucidating the role of plasmids in the development of the gut microbiome and for understanding the impact of plasmid transmission from mother to infant on the health status of infants. Materials and Methods Data set collection In this study, metagenomic data (SRA: PRJNA821542) were obtained and analyzed from a previous study [ 12 ] that tracked gut microbiome associations between mothers and infants using longitudinal multi-omics data. Paired-end read data were downloaded using fasterq-dump (version 3.1.1) with the --split-file option. Analyses were carried out using data from infants at 0.5, 3 and 12 months and from mothers at birth (0 months) corresponding to infants at 0.5 months in this study. Microbiome analysis of shotgun metagenomic sequences Trim Galore pipeline (version 0.6.10) was employed for adapter trimming and quality filtering for the paired-end read data, with default parameters. To remove the human genome from quality-controlled sequences, hg38 was obtained from the UCSC genome browser [ 13 ] and mapped using bowtie2 (version 2.5.4) [ 14 ]. Sequences from which the human genome was removed were assembled using Megahit (version 1.2.9) [ 15 ] independently for each sample. Plasmid detection To identify plasmids in the metagenomic sequences, SCAPP (version 0.1.1) [ 16 ] was run with default parameters. For samples with paired-end reads out of order in forward and reverse, repair was performed with bbmap repair (version 39.01). Protein-coding DNA sequences (CDSs) from plasmid sequences were predicted and functional annotations (gene and product names) were assigned using Bakta (version 1.9.3) [ 17 ]. The plasmids’ mobility type and host range were predicted using MOB-suite (version 3.1.9) with default parameters [ 18 ]. Shared plasmids analysis Plasmid sharing between mother-infant pairs was assessed using BLAST (version 2.16.0) [ 19 ]. For each family, the mother’s plasmids were used to construct a nucleotide database with makeblastdb using the options -dbtype nucl -parse_seqids. The infant’s plasmids served as query sequences in the BLAST search, which was performed with the following parameters: -perc_identity 100, -qcov_hsp_perc 90, -max_hsps 1, and -outfmt 6. Statistical analyses The differences in plasmid counts between infants and mothers, as well as the relationship between infant plasmid counts and delivery mode, were assessed using the Wilcoxon rank-sum test. Additionally, the association between plasmid sharing and delivery mode was analyzed using Fisher’s exact test, based on a contingency table that categorized mother-infant pairs by the occurrence of plasmid sharing and delivery mode. A p -value of ≤ 0.05 was considered statistically significant. Correlations were identified by Spearman’s rank correlation coefficient (significance thresholds were p < 0.05). Results Plasmid Assembly Using Fecal Data from Mothers and Infants We analyzed longitudinal fecal samples from 65 infants and 65 mothers, including 117 mother-infant pairs, to investigate plasmid sharing during the first year of life ( Figure 1A ). Plasmids were identified in mothers and infants across all ages ( Figure 1B ). Mothers tended to harbor more plasmids than infants, particularly pronounced at 0.5 and 3 months of age (Wilcoxon rank-sum test, p < 0.001). When comparing the number of plasmids in infants by delivery mode, those born via vaginal delivery tended to have a higher number of plasmids compared to those delivered by cesarean section, especially at 0.5 months of age, the number of plasmids of the veginal birth group was significantly higher than in the cesarean section group ( Figure 1C ) (Wilcoxon rank-sum test, p = 0.046). Download figure Open in new tab Figure 1. (A) Overview of metagenomic data analysis. Data from mother-infant pairs, when infants were 0.5 months (orange), 3 months (blue), and 12 months (green), were analyzed. (B) Boxplots of plasmid counts for both mothers and infants categorized by infant age. (C) Boxplots of plasmid counts for infants categorized by age and delivery mode. For all panels: **P < 0.001; *P < 0.05. Plasmid Sharing Between Mothers and Infants To infer mother-to-infant plasmid transmission and its influence on the infant microbiome, plasmid sharing between them was analyzed using BLAST with assembled plasmids from both mothers and infants. To ensure the reliability of the analysis, only plasmids showing 100% identity between mothers and infants were considered as shared plasmids. However, given that the sizes of plasmids assembled from short reads may not precisely match the actual plasmid sizes, a minimum coverage threshold of 90% was applied to account for minor differences in plasmid length between mother and infant. Analyses were conducted for infants at the ages of 0.5, 3, and 12 months. Corresponding maternal samples were selected based on the infant’s age. However, for infants aged 0.5 months, maternal plasmid data collected at birth were used, as no maternal samples were available for this time point. Of the 117 pairs compared, 23% (27 pairs) of the infants shared the plasmid with their mothers. The average length of shared plasmids was 4,650±2,039 bp, and their average coverage was 871±1,032×. Plasmids were detected in infants across all age groups; however, shared plasmids between mother-infant pairs were only identified when the infants were 0.5 or 3 months old ( Figure 2 ). No shared plasmids were detected in infants at 12 months of age. Download figure Open in new tab Figure 2. Lineplos showing shared plasmid counts in mother-infant pairs across infant ages. A previous study has shown that the gut microbiome of infants differs depending on the delivery mode (e.g., vaginal birth versus cesarean section) [ 20 ]. To test for differences in shared plasmids by delivery method, the number of shared plasmids in cesarean section and vaginal delivery was examined in 0.5 month infants. At this age, shared plasmids were observed in one out of seven pairs delivered via cesarean section and in 14 out of 42 pairs delivered vaginally (Table 1). However, no statistically significant association was found between delivery mode and plasmid sharing (Fisher’s exact test; p = 0.41). At 3 months, none of the infants delivered via cesarean section had shared plasmids. No plasmid sharing was observed at 12 months of age, regardless of delivery mode, as illustrated in Figure 2 . Host range of shared plasmids and their genetic functions We created a comprehensive host catalog of gut plasmids from infants, containing 228 plasmid contigs based on 27 fecal samples from infants whose plasmid sharing with their mothers was observed. The most striking feature of this catalog was that only 132 of the 228 plasmids (58%) were found in the current databases. Most plasmids were not assigned to specific taxonomic levels, such as species or genus. At the genus level, Bacteroides was predominantly identified among the shared plasmids. At 0.5 months of infant age, plasmids from the Bifidobacterium genus were also detected ( Figure 3 ). Download figure Open in new tab Figure 3. Barplots showing the counts of the host bacteria for shared plasmids, with bar colors corresponding to their taxonomic rank (right). The mobility type of plasmids is considered a key factor in plasmid sharing because mobilizable plasmids appear to transmit from mother to infant more easily than non-mobilizable plasmids and influence early gut microbiome development via horizontal transfer among bacterial cells [ 8 , 21 ]. Therefore, the mobility type of both shared and unshared plasmids was predicted. As a result, no conjugative plasmids were detected for shared plasmids, and the proportion of mobilizable plasmids was higher compared to unshared plasmids (Table S1). To reveal the functional characteristics of shared plasmids in more detail, we compared their functions with unshared plasmids; the CDSs of all plasmids from 27 mother-infant pairs with detected shared plasmids were predicted and annotated. Duplicated genes within a single plasmid were counted as one. The results confirmed that the three most frequently shared genes in the shared plasmids were mbpA, mbpB , and mbpC in Bacteroides . Similarly, these genes were most frequently counted among the plasmid genes found only in mothers. Furthermore, comparing genes identified on maternal plasmids with those shared between mother and offspring showed a trend towards a higher proportion of genes shared by a higher proportion of maternal genes (Spearman correlation, ρ = 0.591, p < 0.01). Persistence of Shared Plasmids in Infants To investigate the influence of plasmid sharing between mother and infant on the infant’s gut bacterial colonization, persistent plasmids in infants—those detectable across multiple ages in the same individual—were analyzed using BLAST, following the same approach applied to identify shared mother-infant plasmids. In an analysis of persistent plasmids between 0.5 and 3 months of age from 39 infants, 32 plasmids were identified as persistent in 21 infants, with four of these plasmids shared between mother and infant at 0.5 months (Figure S1). As shown in Table S3, three of the four shared and persistent plasmids were predicted to be mobilizable and were identified as originating from Bacteroidota or Pseudomonadota . However, the detailed functional characteristics of these four plasmids did not substantially differ from those of other shared plasmids. Discussion Plasmid Assembly Using Fecal Data from Mothers and Infants In this study, plasmids were assembled using fecal data from mothers and infants. The total number of plasmids in infants was generally lower than in mothers, especially at 0.5 and 3 months of age ( Figure 1B ). This may reflect the lower microbiome diversity observed in infants at birth [ 22 ]. However, another study indicated that gut plasmids are highly diverse in early life [ 8 ]. This discrepancy between these findings may be because the previous study restricted plasmid diversity based on the classification of replicase gene types. Plasmid Sharing Between Mothers and Infants Plasmid sharing between mothers and infants was identified using BLAST, representing the first evidence of plasmid transmission from mother to infant. As a result, the number of shared plasmids decreased over time in infants at 0.5, 3, and 12 months ( Figure 2 ). This suggests that as infants grow, the influence of gut bacteria from the mother decreases while the impact of environmental factors and diet increases [ 23 , 24 ]. A previous study [ 25 ] comparing infant and maternal microbiome found that the infant microbiome is generally most similar to the maternal microbiome immediately after birth, supporting the theory of mother-to-infant plasmid transmission during the early postpartum period. Additionally, we compared plasmid sharing rates by delivery mode. Although plasmid sharing was not statistically different by delivery mode, 33% of infants born via vaginal delivery had shared plasmids, which is more than the 14% observed in infants delivered by cesarean section (Table 1). It is important to note that the small sample size of infants delivered by cesarean section may have limited the statistical power of this study. Additionally, the total plasmid counts tended to be higher in infants born via vaginal delivery ( Figure 1C ). A previous study [ 26 ] assessing mother-to-infant microbiome transmission and early life microbiome development estimated a greater influence of the maternal fecal microbiome on infant faecal microbiome in infants born by vaginal delivery compared to those born by cesarean section. In addition to this, a significant association between vaginal delivery and the occurrence of plasmids has also been reported [ 27 ]. The observed higher plasmid sharing rates in vaginal delivery infants may be attributed to the direct exposure to the maternal gut microbiome during birth, which facilitates plasmid-bearing bacteria transmission and their colonization in the infant’s gut. Taxonomic Analysis of Shared Plasmids Plasmids contribute to the formation of the gut microbiome and are known to have diverse effects on the host by interacting with some gut bacteria [ 28 , 29 ]. We predicted their host range to explore the effects of shared plasmids on the gut microbiome ( Figure 3 ). Although we compiled a comprehensive catalog of gut plasmids and their host bacteria from infants, containing 228 plasmid contigs, the host bacteria for only 58% of these contigs could be predicted. This suggests that the plasmid diversity of the gut microbiome has been greatly underestimated, and the plasmids recovered in this study significantly expand our current knowledge of the role of plasmids in the gut environment. As a result of host bacteria predictions of shared plasmids, the only plasmids that could be classified to genus level were associated with Bacteroides and Bifidobacterium , and most plasmids could not be classified to genus ( Figure 3 ). These bacterial genera were reported in a previous study analyzing the same cohort data to be significantly more abundant in mother-to-infant strain transmission [ 12 ]. Additionally, several extensive previous studies have reported that these genera are transmitted from mother to infant and become established over time [ 25 , 26 ]. The large number of plasmids predicted to be hosted by Bacteroides and Bifidobacterium in the shared plasmids is consistent with these previous findings, suggesting that bacteria dominant in the gut environment may facilitate the transmission of many plasmids from mother to infant. Functional Analysis of Shared Plasmids First, plasmid mobility was predicted as one of the most important functions because it is closely linked to plasmid transmission across a wide range of hosts [ 21 ]. As a result, no conjugative plasmids were detected among shared plasmids, and the proportion of mobilizable plasmids was higher compared to unshared plasmids (Table S1). The higher proportion of mobilizable plasmids among shared plasmids may indicate the importance of mobility in plasmid sharing between mothers and infants. However, shared plasmids were identified using a highly conservative method that required 100% identity between mother and infant plasmids. This stringent approach may have led to an underestimation of the count of shared plasmids and their predicted mobility. In particular, larger plasmids, those over 10,000 bp, were more challenging to detect as shared. This may explain why no shared plasmids were identified as conjugative plasmids, which tend to exceed 10,000 bp in size [ 21 ]. On the other hand, of all the plasmids detected, 86% had a genome size of 10,000 bp or less, and the median was 4,630 bp (Figure S2). Therefore it is thought that the potential for sharing most plasmids could be verified using this analysis method. The study showed that plasmids of maternal origin play an important role in the formation of the infant’s gut microbiome through vertical transmission. In particular, among the plasmids shared between mothers and infants, mbpA, mbpB , and mbpC from Bacteroides were found to be the most frequently shared (Table S2). These genes belong to the mbp family and are known to enhance the ability of host bacteria to adapt to their environment by increasing plasmid mobility and facilitating transmission between bacteria [ 30 ]. These genes may play an important role in early gut microbiome development. Furthermore, a positive correlation was observed between the relative proportion of maternal plasmid genes and the proportion shared with the infant. This result indicates that genes with a higher percentage in the mother’s plasmid are more likely to be transmitted to the infant. On the other hand, there was no significant difference in the functional characteristics of the shared and unshared plasmids. These results suggest that plasmid mobility may be a more important factor in transmission than the specific function of the gene. The results of this study emphasize the importance of the gut microbiome of maternal origin on the formation and development of the infant’s gut microbiome. In particular, the mbp gene, which enhances the ability of bacteria to adapt to their environment, may play an important role in the early development of the infant gut microbiome. Persistence of Shared Plasmids in Infants Four plasmids were identified as both shared and persistent in three infants at the age of 0.5 months (Figure S1). The finding that three of these plasmids were predicted to be mobilizable highlights the importance of mobility in plasmid persistence by reducing the likelihood of plasmid loss through horizontal transfer [ 8 , 31 ]. However, these plasmids did not show distinctive functional characteristics compared to other shared plasmids. This suggests that plasmid persistence in infants may occur randomly and infrequently, with the diversity of plasmids in infants dynamically shifting as they grow [ 8 ]. Regarding also the host bacteria diversity, previous research reported that Bacteroides genus is the most specific genus in infant feces and does not become established as these bacteria are usually excreted within hours to days after birth [ 20 , 32 ]. These findings indicate that the influence of shared plasmids on gut microbiome formation in infancy may be immediate rather than long-term. Conclusion In conclusion, we identified shared plasmids between mothers and infants, marking the first evidence of mother-to-infant plasmid transmission. Our findings suggest that plasmid transmission likely occurs during the early postpartum period and is influenced by dominant gut bacteria, aligning with previous research on microbiome transmission [ 12 , 25 ]. This study provides new insights into the mother’s role in shaping the development of the infant’s gut microbiome. Authors contributions YK collected the data set, designed the analysis workflow and performed metagenomic analysis. NS performed genome annotation analysis. KI conceived and supervised the study, designed the analysis workflow and the figures. All authors wrote the manuscript, discussed and approved the manuscript. Conflict of interest statement Kohei Ito is a board member of BIOTA Inc., Tokyo, Japan. Yuki Kuriyama is employed by BIOTA Inc. Tables and figures Table 1. Plasmid sharing ratios by delivery mode and infant age. Each ratio was calculated as the count of mother-infant pairs with plasmid sharing divided by the count of pairs without plasmid sharing. Supplementary Figure 1. Venn diagram of shared and persistent plasmid counts in infants at 0.5 months. Shared plasmids were identified by comparing plasmids between mothers and their infants at 0.5 months, while persistent plasmids were determined by tracking the same plasmids in infants between 0.5 and 3 months of age. Supplementary Figure 2. Histogram showing the size distribution of shared and unshared plasmids. Supplementary Table 1, Counts of mobility type about both shared and unshared plasmids. Supplementary Table 2. This table summarizes the number of plasmid genes detected in the maternal and shared microbiomes at 0.5 months. Supplementary Table 3. Details of shared and persistent plasmids in infants at 0.5 months. The sequence coverage, predicted mobility, and host range are presented for each plasmid. Acknowledgements All authors thank Morgenrot Inc. for providing the computational environment for the analysis. We would like to express our sincere gratitude to the authors of the previous studies included in our meta-analysis, particularly Dr. Vatanen and Dr. Xavier, for their generous cooperation in providing additional data. Refferences 1. ↵ Afzaal H Shahiq-Uz-Zaman , Saeed A , Hamdani SDA , Raza A , Gul A , et al. Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue . Front Pharmacol . 2022 ; 13 : 1017549 . OpenUrl CrossRef PubMed 2. ↵ Li C , Chen J , Li SC . Understanding Horizontal Gene Transfer network in human gut microbiota . Gut Pathog . 2020 ; 12 : 33 . OpenUrl CrossRef PubMed 3. ↵ Carattoli A. Plasmids and the spread of resistance . Int J Med Microbiol . 2013 ; 303 : 298 – 304 . OpenUrl CrossRef PubMed 4. ↵ Dominguez-Bello MG , Costello EK , Contreras M , Magris M , Hidalgo G , Fierer N , et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns . Proc Natl Acad Sci U S A . 2010 ; 107 : 11971 – 11975 . OpenUrl Abstract / FREE Full Text 5. ↵ Pärnänen K , Karkman A , Hultman J , Lyra C , Bengtsson-Palme J , Larsson DGJ , et al. Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements . Nat Commun . 2018 ; 9 : 3891 . OpenUrl CrossRef PubMed 6. Laursen MF , Sakanaka M , von Burg N , Mörbe U , Andersen D , Moll JM , et al. Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut . Nat Microbiol . 2021 ; 6 : 1367 – 1382 . OpenUrl CrossRef PubMed 7. Praveen P , Jordan F , Priami C , Morine MJ . The role of breast-feeding in infant immune system: a systems perspective on the intestinal microbiome . Microbiome . 2015 ; 3 : 41 . OpenUrl CrossRef PubMed 8. ↵ He W , Russel J , Klincke F , Nesme J , Sørensen SJ . Insights into the ecology of the infant gut plasmidome . Nat Commun . 2024 ; 15 : 6924 . OpenUrl CrossRef PubMed 9. ↵ Mitchell CM , Mazzoni C , Hogstrom L , Bryant A , Bergerat A , Cher A , et al. Delivery mode affects stability of early infant gut Microbiota . Cell Rep Med . 2020 ; 1 : 100156 . OpenUrl CrossRef PubMed 10. ↵ Selma-Royo M , Calatayud Arroyo M , García-Mantrana I , Parra-Llorca A , Escuriet R , Martínez-Costa C , et al. Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function . Microbiome . 2020 ; 8 : 167 . OpenUrl CrossRef PubMed 11. ↵ Salminen S , Gibson GR , McCartney AL , Isolauri E. Influence of mode of delivery on gut microbiota composition in seven year old children . Gut . 2004 ; 53 : 1388 – 1389 . OpenUrl FREE Full Text 12. ↵ Vatanen T , Jabbar KS , Ruohtula T , Honkanen J , Avila-Pacheco J , Siljander H , et al. Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism . Cell . 2022 ; 185 : 4921 – 4936 .e15. OpenUrl CrossRef PubMed 13. ↵ Raney BJ , Barber GP , Benet-Pagès A , Casper J , Clawson H , Cline MS , et al. The UCSC Genome Browser database: 2024 update . Nucleic Acids Res . 2024 ; 52 : D1082 – D1088 . OpenUrl CrossRef PubMed 14. ↵ Langmead B , Salzberg SL . Fast gapped-read alignment with Bowtie 2 . Nat Methods . 2012 ; 9 : 357 – 359 . OpenUrl CrossRef PubMed Web of Science 15. ↵ Li D , Liu C-M , Luo R , Sadakane K , Lam T-W. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph . Bioinformatics . 2015 ; 31 : 1674 – 1676 . OpenUrl CrossRef PubMed 16. ↵ Pellow D , Zorea A , Probst M , Furman O , Segal A , Mizrahi I , et al. SCAPP: an algorithm for improved plasmid assembly in metagenomes . Microbiome . 2021 ; 9 : 144 . OpenUrl CrossRef PubMed 17. ↵ Schwengers O , Jelonek L , Dieckmann MA , Beyvers S , Blom J , Goesmann A. Bakta: rapid and standardized annotation of bacterial genomes via alignment-free sequence identification . Microb Genom . 2021 ; 7 . doi: 10.1099/mgen.0.000685 OpenUrl CrossRef PubMed 18. ↵ Robertson J , Nash JHE . MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies . Microb Genom . 2018 ; 4 . doi: 10.1099/mgen.0.000206 OpenUrl CrossRef PubMed 19. ↵ Altschul SF , Gish W , Miller W , Myers EW , Lipman DJ . Basic local alignment search tool . J Mol Biol . 1990 ; 215 : 403 – 410 . OpenUrl CrossRef PubMed Web of Science 20. ↵ Chu DM , Ma J , Prince AL , Antony KM , Seferovic MD , Aagaard KM . Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery . Nat Med . 2017 ; 23 : 314 – 326 . OpenUrl CrossRef PubMed 21. ↵ Smillie C , Garcillán-Barcia MP , Francia MV , Rocha EPC , de la Cruz F. Mobility of plasmids . Microbiol Mol Biol Rev . 2010 ; 74 : 434 – 452 . OpenUrl Abstract / FREE Full Text 22. ↵ Hill CJ , Lynch DB , Murphy K , Ulaszewska M , Jeffery IB , O’Shea CA , et al. Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort . Microbiome . 2017 ; 5 : 4 . OpenUrl CrossRef PubMed 23. ↵ Shi Y , Yin R , Pang J , Chen Y , Li Z , Su S , et al. Impact of complementary feeding on infant gut microbiome, metabolites and early development . Food Funct . 2024 ; 15 : 10663 – 10678 . OpenUrl CrossRef PubMed 24. ↵ Nielsen CC , Gascon M , Osornio-Vargas AR , Shier C , Guttman DS , Becker AB , et al. Natural environments in the urban context and gut microbiota in infants . Environ Int . 2020 ; 142 : 105881 . OpenUrl CrossRef PubMed 25. ↵ Browne HP , Shao Y , Lawley TD . Mother-infant transmission of human microbiota . Curr Opin Microbiol . 2022 ; 69 : 102173 . OpenUrl CrossRef PubMed 26. ↵ Wang S , Zeng S , Egan M , Cherry P , Strain C , Morais E , et al. Metagenomic analysis of mother-infant gut microbiome reveals global distinct and shared microbial signatures . Gut Microbes . 2021 ; 13 : 1 – 24 . OpenUrl CrossRef PubMed 27. ↵ Ravi A , Valdés-Varela L , Gueimonde M , Rudi K. Transmission and persistence of IncF conjugative plasmids in the gut microbiota of full-term infants . FEMS Microbiol Ecol . 2018 ; 94 : fix158 . OpenUrl 28. ↵ Zhang P , Mao D , Gao H , Zheng L , Chen Z , Gao Y , et al. Colonization of gut microbiota by plasmid-carrying bacteria is facilitated by evolutionary adaptation to antibiotic treatment . ISME J . 2022 ; 16 : 1284 – 1293 . OpenUrl CrossRef PubMed 29. ↵ - Yang L , Mai G , Hu Z , Zhou H , Dai L , Deng Z , et al. Global transmission of broad-host-range plasmids derived from the human gut microbiome . Nucleic Acids Res . 2023 ; 51 : 8005 – 8019 . OpenUrl CrossRef PubMed 30. ↵ Novicki TJ , Hecht DW . Characterization and DNA sequence of the mobilization region of pLV22a from Bacteroides fragilis . J Bacteriol . 1995 ; 177 : 4466 – 4473 . OpenUrl Abstract / FREE Full Text 31. ↵ Lopatkin AJ , Meredith HR , Srimani JK , Pfeiffer C , Durrett R , You L. Persistence and reversal of plasmid-mediated antibiotic resistance . Nat Commun . 2017 ; 8 : 1689 . OpenUrl CrossRef PubMed 32. ↵ Enav H , Bäckhed F , Ley RE . The developing infant gut microbiome: A strain-level view . Cell Host Microbe . 2022 ; 30 : 627 – 638 . OpenUrl CrossRef PubMed View the discussion thread. Back to top Previous Next Posted December 20, 2024. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria Yuki Kuriyama , Natsuki Suganuma , Kohei Ito bioRxiv 2024.12.19.629351; doi: https://doi.org/10.1101/2024.12.19.629351 Share This Article: Copy Citation Tools Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria Yuki Kuriyama , Natsuki Suganuma , Kohei Ito bioRxiv 2024.12.19.629351; doi: https://doi.org/10.1101/2024.12.19.629351 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Microbiology Subject Areas All Articles Animal Behavior and Cognition (7649) Biochemistry (17738) Bioengineering (13925) Bioinformatics (42059) Biophysics (21496) Cancer Biology (18643) Cell Biology (25577) Clinical Trials (138) Developmental Biology (13406) Ecology (19946) Epidemiology (2067) Evolutionary Biology (24370) Genetics (15627) Genomics (22551) Immunology (17772) Microbiology (40497) Molecular Biology (17212) Neuroscience (88786) Paleontology (667) Pathology (2845) Pharmacology and Toxicology (4835) Physiology (7663) Plant Biology (15177) Scientific Communication and Education (2047) Synthetic Biology (4304) Systems Biology (9838) Zoology (2272)