Summary
The sterile womb paradigm is an enduring premise in biology that human infants are
born sterile. Recent studies suggest that infants incorporate an initial microbiome
before birth and receive copious supplementation of maternal microbes through birth
and breastfeeding. Moreover, evidence for microbial maternal transmission is increasingly
widespread across animals. This collective knowledge compels a paradigm shift—one
in which maternal transmission of microbes advances from a taxonomically specialized
phenomenon to a universal one in animals. It also engenders fresh views on the assembly
of the microbiome, its role in animal evolution, and applications to human health
and disease.
Introduction
While the human microbiota comprises only 1–3% of an individual's total body mass,
this small percentage represents over 100 trillion microbial cells, outnumbering human
cells 10 to 1 and adding over 8 million genes to our set of 22,000 [1],[2]. This complexity
establishes a network of interactions between the host genome and microbiome spanning
gut development [3], digestion [4],[5], immune cell development [6]–[8], dental health
[9],[10], and resistance to pathogens [11],[12]. Recent studies have also provided
a greater understanding of how the composition of an individual's microbiota changes
throughout development, especially during the first year of life [3],[13]. While the
general dogma is that the placental barrier keeps infants sterile throughout pregnancy,
increasing evidence suggests that an infant's initial inoculum can be provided by
its mother before birth [14]–[18] and is supplemented by maternal microbes through
the birthing [19] and breastfeeding [20],[21] processes.
While maternal transmission of microbes in humans has attracted considerable attention
in the last few years, nearly a century's worth of research is available for vertical
transmission of symbionts in invertebrates [22]. Similar to gut bacteria in humans
that assist nutrient intake, many insect-associated bacteria function as nutritional
symbionts that supplement the nutrient-poor diet of their host with essential vitamins
or amino acids [23],[24]. Since these indispensable symbionts cannot live outside
of host cells, they cannot be acquired from the environment and are faithfully transferred
from mother to offspring [22],[25]. Maternal transmission in invertebrates has been
reviewed elsewhere [22],[26],[27], and Box 1 and Box 2 highlight examples of heritable
symbioses across invertebrate phyla.
Box 1. Examples of Maternal Transmission in Marine Invertebrates
Marine Sponges (Phylum Porifera)
Sponges are ancient metazoans that evolved over 600 million years ago as one of the
first multicellular animals [83]. In marine sponges, a remarkably large consortium
of extracellular microbial symbionts thrives within the sponge's mesohyl, a gelatinous
connective tissue located between the external and internal cell layers. Many of these
bacterial residents are found in diverse species of sponges with nonoverlapping distributions
but not in the surrounding seawater [84]–[86]. These “sponge-specific” microbes are
hypothesized to have originated from ancient colonization events before the diversification
of marine sponges and are maintained as symbionts through vertical transmission [87].
Independent studies have estimated that up to 33 phylogenetically distinct microbial
clusters spanning ten bacterial phyla and one archaeal phylum are vertically transmitted
in sponges [41],[84],[86],[88]. Both transmission electron microscopy (TEM) and fluorescent
in situ hybridization (FISH) studies have confirmed the presence of microorganisms
of different shapes and sizes in the oocytes of oviparous sponges [41] and in the
embryos of viviparous sponges [43]–[45].
Vesicomyid Clams (Phylum Mollusca)
Deep-sea hydrothermal vent communities rely upon chemosynthetic bacteria to harness
chemical energy stored in reduced sulfur compounds extruding from the vents. Metazoans
that live in this extreme environment harbor chemosynthetic endosymbionts in their
tissues that provide most, if not all, of the host's nutrition [89]. Somewhat surprisingly,
most invertebrates that live near hydrothermal events acquire their endosymbionts
anew from the environment each generation [90],[91], even though chemosynthetic bacteria
are crucial for survival in such a harsh habitat. A major exception to this trend
is found in the Vesicomyidae family of clams [92]. Vesicomyid clams retain a rudimentary
gut and rely primarily on sulfur-oxidizing bacteria sequestered intracellularly within
specialized host cells called bacteriocytes in the clam's large, fleshy gills [93].
Vertical transmission via transovarial transmission appears to be the dominant mechanism
for maintenance of these thioautotrophic bacterial symbionts given that follicle cells
surrounding an oocyte and the oocyte itself are heavily infected with the chemosynthetic
bacteria [46],[94].
Box 2. Examples of Maternal Transmission in Terrestrial Invertebrates
Insects (Phylum Arthropoda)
Insects that thrive on unbalanced diets such as plant sap, blood, or wood depend upon
microbial symbionts for the provision of essential amino acids or vitamins lacking
in their food source. In turn, hosts provide a wide range of metabolites to their
symbionts as well as protection from environmental stressors. This codependence requires
faithful transfer of symbionts to all offspring, usually through transovarial transmission
[23],[24]. Reproductive parasites, such as the obligate, intracellular bacteria Wolbachia,
are also widespread in insects and hijack maternal transmission routes to ensure their
spread within an insect population (reviewed in [95],[96]).
Pea Aphid (Acrythosiphon pisum)
The pea aphid Acrythosiphon pisum (Figure 2A) and its nutritional endosymbiont Buchnera
aphidicola are a preeminent example of obligate mutualism in insects. The ancestral
Buchnera gammaproteobacteria was acquired by aphids between 160 and 280 million years
ago [97] and has since diverged in parallel with its aphid hosts through strict vertical
transmission [26],[97]. Buchnera are housed within the cytoplasm of bacteriocytes
arranged into dual bacteriome structures located in the aphid body cavity adjacent
to the ovaries [98], allowing efficient transfer of Buchnera symbionts to developing
oocytes or embryos during the sexual and asexual phases of aphid reproduction, respectively.
At the cellular level, symbiont transfer occurs when maternal bacteriocytes release
Buchnera symbionts through exocytosis into the extracellular space between the bacteriocyte
and oocyte or embryo, which then actively endocytoses the extracellular Buchnera symbionts
[51].
Cockroaches (Order Blattodea)
Just as insects are morphologically diverse, the mechanisms by which insects transport
symbionts to oocytes are highly varied. In cockroaches, Blattabacterium-filled bacteriocyte
cells migrate from the abdominal fat body to the distantly located ovarioles where
they adhere to the oocyte membrane [99],[100]. Interestingly, the bacteriocytes remain
associated with the oocyte for eight to nine days before finally expelling their symbionts
through exocytosis. The Blattabacterium cells then squeeze between the follicle cells
surrounding the oocyte and are engulfed into the oocyte cytoplasm via endocytosis
just prior to ovulation [100].
Whiteflies (Family Aleyrodidae)
The whitefly circumvents exocytosis of its intracellular nutritional symbiont, Portiera
aleyrodidarum, by depositing entire bacteriocytes into its eggs. These maternal bacteriocytes
remain intact yet separate from the developing embryo until the embryonic bacteriomes
form, at which point the maternal bacteriocytes deteriorate [22].
Tsetse Flies, Bat Flies, and Louse Flies (Superfamily Hippoboscoidea)
Members of the Hippoboscoidea superfamily (Order Diptera) are obligate blood feeders
that have developed a unique reproductive strategy termed adenotrophic viviparity
that offers a different solution to internal maternal transfer of symbionts. Females
of this superfamily develop a single fertilized embryo at a time within their uterus
(modified vaginal canal) until it is deposited as a mature third instar larva immediately
preceding pupation. During their internal development, the larvae are nourished with
milk produced by modified accessory glands that empty into the uterus [101]. The milk
primarily consists of protein and lipids [102], but it also serves as a reservoir
for maternally transmitted microbial symbionts [103]. For example, the obligate mutualistic
symbiont of tsetse flies, Wigglesworthia glossinidia, is absent from the female germ
line and surrounding reproductive tissues but is found extracellularly in the female
milk glands and is first detected in tsetse offspring once milk consumption begins
during the first larval stage [103].
Stinkbugs (Superfamily Pentatomoidea)
One of the most common mechanisms of external maternal transmission in insects is
that of “egg smearing,” which occurs when a female contaminates the surface of her
eggs with symbiont-laden feces during oviposition. Upon hatching, offspring probe
or consume the discarded egg shells to acquire the maternal bacteria. This mode of
transmission is commonly found in plant-sucking stinkbugs, including the Pentatomidae
and Acanthosomatidae families [104]. In the Cynidae family of stinkbugs, along with
the Coreidae family of leaf-footed bugs, gut symbionts are transferred maternally
via coprophagy, in which offspring consume maternal feces, sometimes directly from
the mother's anus [22],[104]. Stinkbugs of the Plataspidae family, on the other hand,
have developed a unique mode of transmission via a maternally provided “symbiont capsule”
deposited on the underside of the egg mass [56]. These capsules are comprised of bacterial
cells dispersed throughout a resin-like matrix surrounded by a brown, cuticle-like
envelope that protects the symbionts from environmental stressors such as UV irradiation
or dissection [57]. After hatching, plataspid nymphs immediately probe the capsules
to ingest the symbionts [56],[59].
European Beewolf (Philanthus triangulum)
While nutritional symbionts appear to be the most common type of bacteria transmitted
via external maternal transmission in insects, the European beewolf (Philanthus triangulum)
instead cultivates a symbiotic bacteria that protects offspring against microbial
infection during development. Beewolves are solitary digger wasps that deposit their
offspring in moist, underground nests, making them susceptible to fungal and bacterial
infections [105]. To combat these pathogens, female beewolves cultivate Streptomyces
philanthi bacteria in specialized glands in their antennae, which they copiously spread
on the ceiling of the brood cell before oviposition [106]–[108]. After hatching, the
larvae take up the bacterial cells and incorporate them into their cocoon that they
build before pupation. When adult beewolves emerge from their cocoon in the summer,
female beewolves acquire the maternally provided Streptomyces symbiont and house them
in the female-specific gland reservoirs along each antenna [108],[109].
By integrating previous studies in invertebrates with recent evidence for maternal
microbial transmission in humans and other vertebrates, we contend that maternal provisioning
of microbes is a universal phenomenon in the animal kingdom. As a result, a considerable
new phase of study in heritable symbiont transmission is underway. Thus, this essay
presents current evidence for maternal microbial transmission and provides new insights
into its impact on microbiome assembly and evolution, with applications to human health
and disease.
Internal Maternal Transmission
At the turn of the twentieth century, French pediatrician Henry Tissier asserted that
human infants develop within a sterile environment and acquire their initial bacterial
inoculum while traveling through the maternal birth canal [28]. More than a century
later, the sterile womb hypothesis remains dogma, as any bacterial presence in the
uterus is assumed to be dangerous for the infant. Indeed, studies of preterm deliveries
have found a strong correlation between intrauterine infections and preterm labor,
especially when birth occurs less than 30 weeks into the pregnancy [29],[30]. Since
preterm birth is the leading cause of infant mortality worldwide [31], much attention
has focused on identifying the bacterial culprits responsible for spontaneous preterm
labor. Surprisingly, most of the bacteria detected in intrauterine infections are
commonly found in the female vaginal tract [29], and risk of preterm birth is markedly
increased in women diagnosed with bacterial vaginosis during pregnancy [32]. Interestingly,
the vaginal microbial community varies significantly among American women of different
ethnicities (Caucasian, African-American, Asian, or Hispanic), with African-American
and Hispanic women more likely to have a microbiota traditionally associated with
bacterial vaginosis (predominance of anaerobic bacteria over Lactobacillus species)
[33] and a higher rate of spontaneous preterm deliveries (reviewed in [34]).
While intrauterine infection and inflammation is important in understanding the etiology
of preterm birth, relatively few studies have examined the uterine microbiome of healthy,
term pregnancies owing to the sterile womb paradigm. Investigations into the potential
for bacterial transmission through the placental barrier have detected bacteria in
umbilical cord blood [17], amniotic fluid [14],[35], and fetal membranes [35],[36]
from babies without any indication of inflammation (Figure 1). Furthermore, an infant's
first postpartum bowel movement of ingested amniotic fluid (meconium) is not sterile
as previously assumed, but instead harbors a complex community of microbes, albeit
less diverse than that of adults [18],[37]. Interestingly, many of the bacterial genera
found in the meconium, including Enterococcus and Escherichia, are common inhabitants
of the gastrointestinal tract [18],[37]. To test whether maternal gut bacteria can
be provisioned to fetuses in utero, Jiménez et al.
[18] fed pregnant mice milk inoculated with genetically-labeled Enterococcus faecium
and then examined the meconium microbes of term offspring after sterile C-section.
Remarkably, E. faecium with the genetic label was cultured from the meconium of pups
from inoculated mothers, but not from pups of control mice fed noninoculated milk.
Meconium from the treatment group also had a higher abundance of bacteria than that
of the control group. Importantly, the study controlled for potential bacterial contamination
from contact between skin and the meconium by sampling an internal portion of the
meconium [18]. Thus, this study provides foundational evidence for maternal microbial
transmission in mammals.
10.1371/journal.pbio.1001631.g001
Figure 1
Sources of microbial transmission in humans from mother to child.
Cut-away diagram highlighting the various internal and external sources of maternal
microbial transmission as well as the species that are commonly associated with transfer
from those regions. Regions discussed include the oral cavity [14],[16], the mammary
glands [40],[78],[79], the sebaceous skin surrounding the breast [78],[80], the vaginal
tract [19],[33],[73], and the intrauterine environment [14],[15],[17],[18],[29],[35]–[37],[40].
Illustration by Robert M. Brucker.
Other than ascension of vaginal microbes associated with preterm births, the mechanisms
by which gut bacteria gain access to the uterine environment are not well understood.
One possibility is that bacteria travel to the placenta via the bloodstream after
translocation of the gut epithelium. While the intestinal epithelial barrier generally
prevents microbial entry into the circulatory system, dendritic cells can actively
penetrate the gut epithelium, take up bacteria from the intestinal lumen, and transport
the live bacteria throughout the body as they migrate to lymphoid organs [38],[39].
Interestingly, microbial translocation may even increase during pregnancy, as one
study showed that pregnant mice were 60% more likely to harbor bacteria in their mesenteric
lymph node (presumably brought there by dendritic cells) than nonpregnant mice [40].
Bacterial species normally found in the human oral cavity have also been isolated
from amniotic fluid and likely enter the bloodstream during periodontal infections,
facilitated by gingiva inflammation [14],[16] (Figure 1).
Overall, the study of internal maternal transmission of microbes in mammals is in
its infancy due to the enduring influence of the sterile womb paradigm and to the
ethical and technical difficulties of collecting samples from healthy pregnancies
before birth. Thus, we still know very little about the number and identity of innocuous
microbes that traverse the placenta, whether they persist in the infant, or whether
their presence has long-term health consequences for the child. Similarly, we know
almost nothing about nonpathogenic viruses or archaea that may be transferred from
mother to child alongside their bacterial counterparts. Fortunately, the advent of
culture-independent, high-throughput sequencing will serve as a tremendous resource
for this field and will hopefully lead to a characterization of the “fetal microbiome”
in utero.
Maternal provisioning of microbes to developing offspring is widespread in animals,
with evidence of internal microbial transmission in animal phyla as diverse as Porifera
[41]–[45] (Box 1), Mollusca [46]–[49] (Box 1), Arthropoda [50]–[52] (Box 2, Figure
2), and Chordata [19],[53],[54] (Box 3, Figure 2). The presence of maternal transmission
at the base of the Animalia kingdom and the surprising plasticity by which microbes
gain access to germ cells or embryos in these systems signifies that maternal symbiont
transmission is an ancient and evolutionarily advantageous mechanism inherent in animals,
including humans. Therefore, we can no longer ignore the fact that exposure to microbes
in the womb is likely and may even be a universal part of human pregnancy, serving
as the first inoculation of beneficial microbes before birth.
10.1371/journal.pbio.1001631.g002
Figure 2
Examples of animals that exhibit microbial maternal transmission.
(A) Pea aphid (Acyrthosiphon pisum), photo credit: Whitney Cranshaw, Colorado State
University/©Bugwood.org/CC-BY-3.0-US; (B) Domesticated chicken hen (Gallus gallus
domesticus), photo credit: Ben Scicluna; (C) Sockeye salmon (Oncorhynchus nerka),
photo credit: Cacophony; (D) South American river turtle (Podocnemis expansa), photo
credit: Wilfredor. All photos were obtained from Wikimedia Commons (www.commons.wikimedia.org).
Box 3. Examples of Maternal Transmission in Vertebrates
Aside from studies in human and mouse models, very little is known about maternal
transmission of microbial communities in vertebrates, especially outside Class Mammalia.
Furthermore, research on vertical transmission in nonmammalians has largely focused
on maternally transmitted pathogens, especially in animals of agricultural importance
like chickens and fish.
Domesticated Chickens (Gallus gallus domesticus)
Zoonotic Salmonella infections acquired from contaminated chicken eggs is estimated
to cause more than 100,000 illnesses each year in the United States [110]. In addition
to horizontal transmission of Salmonella on eggs through surface contamination, direct
transovarial transmission also occurs when Salmonella colonizes the reproductive tissues
of hens (Figure 2B). Depending on the infection location within the female reproductive
tract, the bacteria are deposited into the yolk, albumen, eggshell membrane, and/or
eggshell of the developing egg before oviposition (reviewed in [111]). Other poultry
pathogens, such as Mycoplasma synoviae in chickens [112] and M. gallisepticum, M.
cloacale, and M. anatis in ducks [113], have also been cultured from the yolk of embryonated
eggs, though whether commensal flora are incorporated into the egg is not known.
Ray-Finned Fish (Class Actinopterygii)
Several bacterial pathogens of economically important fish are transmitted transovarially
in the egg yolk including Renibacterium salmoninarum, the agent of bacterial kidney
disease in salmonids (Figure 2C), and Flavobacterium psychrophilum, which causes bacterial
cold water disease in salmonids and rainbow trout fry disease in trout (reviewed in
[114]). F. psychrophilum has also been found in ovarian fluid and on the surface of
eggs of steelhead trout [115]. Additionally, an obligate, intracellular eukaryotic
parasite, Pseudoloma neurophilia, is a common pathogen found in zebrafish (Danio rerio)
facilities and has been observed in spores of the ovarian stroma and within developing
follicle cells of spawning females, suggesting that it can be vertically transmitted,
though it is primarily spread from fish to fish in contaminated water (reviewed in
[116]).
Turtles (Order Chelonii)
The formation of egg components in the uterine tube and uterus of turtles takes approximately
two weeks, providing ample opportunity for maternal transmission of intestinal or
reproductive microbes to the egg [117]. One study of unhatched (dead) eggs from loggerhead
sea turtle (Caretta caretta) nests found several potential pathogens, including Pseudomonas
aeruginosa and Serratia marcesans, in fluid from the interior of the eggs, though
environmental contamination of the eggs cannot be ruled out [118]. A similar study
of eggs from two species of South American river turtles, Podocnemis expansa (Figure
2D) and P. unifilis, identified several Enterobacteriaceae species, including Escherichia
coli, Shigella flexneri, and Salmonella cholerasuis, in the eggs but not in the environmental
samples taken from the turtle nests [119], suggesting that they may have a maternal
origin. In support of this hypothesis, a separate study in green turtles (Chelonia
mydas) that collected eggs directly from the maternal cloacal opening during egg laying
isolated Pseudomonas, Salmonella, Enterobacter, and Citrobacter from the eggshell,
albumen, and yolk. In fact, the yolk was the egg component most heavily infected with
bacteria [120]. Altogether, many potentially pathogenic species have been isolated
from turtle eggs, but whether these bacteria actually cause disease in turtles or
are part of their natural flora remains to be determined.
External Maternal Transmission
External maternal transmission encompasses any transfer of maternal symbionts to offspring
during or after birth. In invertebrates, it is often accomplished by “egg smearing,”
in which females coat eggs with microbes as they are deposited [55], or through the
provision of a microbe-rich maternal fecal pellet that is consumed by larval offspring
upon hatching [56]–[59] (see Box 2). Similarly, human infants are “smeared” with maternal
vaginal and fecal microbes as they exit the birth canal [60]–[62] (Figure 1). Several
studies have shown that the human neonatal microbiota across all body habitats (skin,
oral, nasopharyngeal, and gut) is influenced by their mode of delivery [19],[63]–[65],
with infants born vaginally acquiring microbes common in the female vagina while C-section
infants display a microbiota more similar to that of human skin [19]. Furthermore,
while the microbiota of a vaginally delivered infant clusters with the vaginal bacteria
of its mother, the microbiota of C-section babies is no more related to the skin flora
of its mother than that of a stranger, indicating that most microbes are transmitted
to the neonate from those handling the infant [19]. Importantly, epidemiological data
suggest that a Cesarean delivery can have long-term consequences on the health of
a child, especially concerning immune-mediated diseases. For example, children born
via C-section are significantly more likely to develop allergic rhinitis [66], asthma
[66], celiac disease [67], type 1 diabetes [68], and inflammatory bowel disease [69].
These statistics are alarming given that 32.8% of all births in the United States
in 2010 were delivered via C-section with similar rates on the rise in most developed
countries [70].
The higher rate of immune-mediated diseases in C-section children may indicate that
maternally transferred vaginal or fecal microbes are unique in their ability to elicit
immune maturation in the neonate. Development of the intestinal mucosa and secondary
lymphoid tissues in the gut is contingent upon recognition of microbial components
by pattern-recognition receptors on intestinal epithelial cells (reviewed in [71],[72]).
It is possible that these receptors cannot properly interact with the community of
microbes acquired during Cesarean deliveries, leading to disrupted immune development
and an increased risk for immune-mediated disorders in C-section children. Conversely,
transmission for thousands of years of vaginal and fecal microbes at birth has likely
produced specific human-microbe interactions important for neonatal gut development.
In fact, a recent study found that the vaginal microbial community changes during
pregnancy, becoming less diverse as the pregnancy progresses [73]; yet, in spite of
the general decrease in richness, certain Lactobacillus bacterial species are enriched
in the vaginal community during pregnancy and are hypothesized to be important for
establishing the neonatal upper GI microbiota after vaginal delivery [73].
Breastfeeding provides a secondary route of maternal microbial transmission as shown
in humans (reviewed in [74], Figure 1) and nonhuman primates such as rhesus monkeys
[75]. In humans, maternal milk microbes are implicated in infant immune system development
[76], resistance against infection [77], and protection against the development of
allergies and asthma later in childhood [74]. High-throughput sequencing of breast
milk from 16 healthy women identified 100–600 species of bacteria in each sample with
nine genera present in every sample: Staphylococcus, Streptococcus, Serratia, Pseudomonas,
Corynebacterium, Ralstonia, Propionibacterium, Sphingomonas, and Bradyrhizobiaceae
[78]. This “core” milk microbiome represented approximately 50% of all bacteria in
each sample, with the other half representing individual variation in microbial composition
[78]. A similar study found that the bacterial composition in breast milk changes
over time: milk produced immediately after labor harbored more lactic acid bacteria
along with Staphylococcus, Streptococcus, and Lactococcus, while breast milk after
six months of lactation had a significant increase in typical inhabitants of the oral
cavity, such as Veillonella, Leptotrichia, and Prevotella
[79], perhaps to prime the infant for the switch to solid food. However, as with any
DNA-based, culture-independent study that does not discriminate between live and dead
bacteria, the number and identity of bacteria detected in these studies should be
interpreted with some caution.
Given that milk is only produced temporarily in a woman's life, the origin of milk
microbes is still somewhat of a mystery. Breast milk was traditionally thought to
be sterile; however, colostrum (the first milk produced after delivery) collected
aseptically already harbors hundreds of bacterial species [79]. Breast milk does share
many taxa with the microbiota found on sebaceous skin tissue around the nipple [78],[80],
and high levels of Streptococcus in breast milk may be a result of retrograde flow
from an infant's oral cavity back to the milk ducts during suckling [81] since Streptococcus
is the dominant phylotype in infant saliva [82]. However, the presence of anaerobic
gut bacteria in human milk suggests that an entero-mammary route of transfer also
exists that may utilize phagocytic dendritic cells to traffic gut microbes to the
mammary glands, similar to microbial transfer to amniotic fluid as discussed earlier.
To support this hypothesis, Perez et al.
[40] found identical strains of bacteria in milk cells, blood cells, and fecal samples
from lactating women, but more work is needed to directly connect bacterial translocation
in the gut to incorporation in breast milk.
Overall, maternal transmission of beneficial microbes in humans has widespread relevance
for human health. Evolution with these microbes has resulted in our dependence on
them for the proper maturation and development of the immune system and gastrointestinal
tract. Somewhat paradoxically, modern medicine designed to prevent infant mortality
(such as emergency Cesarean sections and formula feeding) has likely contributed to
the rise in immune-mediated diseases in developed countries due to the inherent lack
of exposure to maternal microbes associated with these practices. Fortunately, biomedicine
is also making strides in finding effective probiotic supplements to promote immune
development and ameliorate some of the risks that C-section or formula-fed infants
face as children and adults. Hopefully, as we gain understanding of the diversity
and function of maternally transmitted microbes in humans, more complete and effective
probiotic blends will recapitulate the microbial communities found in vaginally delivered,
breast-fed infants and restore the microbe-host interactions that humans depend upon
for proper development.
Conclusions
Since the early twentieth century, the study of maternal microbial transmission has
focused heavily on animal systems in which maternal transmission maintains sophisticated
partnerships with one or two microbial species. However, with the development of high-throughput
sequencing technologies, it is now possible to identify entire microbiomes that are
transferred from mother to offspring in systems not traditionally considered to exhibit
maternal transmission, such as humans. By expanding the definition of maternal transmission
to include all internal and external microbial transfers from mother to offspring,
we contend that maternal transmission is universal in the animal kingdom and is used
to provision offspring with important microbes at birth, rather than leave their acquisition
to chance.
Finally, with microbes contributing 99% of all unique genetic information present
in the human body, maternal microbial transmission should be viewed as an additional
and important mechanism of genetic and functional change in human evolution. Similar
to deleterious mutations in our genetic code, disruption of maternal microbial acquisition
during infancy could “mutate” the composition of the microbial community, leading
to improper and detrimental host-microbe interactions during development. Maternal
transmission is also a key factor in shaping the structure of the microbiome in animal
species over evolutionary time, since microbes that promote host fitness, especially
in females, will simultaneously increase their odds of being transferred to the next
generation. Thus, whether internal or external, the universality and implications
of maternal microbial transmission are nothing short of a paradigm shift for the basic
and biomedical life sciences.