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Maternity and the Microbiome

The important role of the gut microbiome in every aspect of the health & development of our children

The health, diet, and genetics of the parents, along with birthing method, breast feeding, antibiotic use, & early diet of the child, have major impacts on the health and development of the child.


General maternity wiki here: https://github.com/MaximilianKohler/Archive/wiki/Maternity

General:

Reviews on establishment and impact of gut microbiome on development & later health: [2019][2018][2018][2018][2017][2016][2018]

Genetics have a major impact on the gut microbiome.

Key window in early life: Early, but not late life engraftment of a single dominant Bacteroides strain of non-antibiotic treated IL-10-/- mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL-10-/- mice that had antibiotic-induced dysbiosis (Jun 2021) https://www.eurekalert.org/pub_releases/2021-06/uocm-rgm060721.php

Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation (Jan 2020, n=152 women, and mice) https://gut.bmj.com/content/early/2020/01/02/gutjnl-2019-319101 "This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis"

The microbiota of the pregnant woman can vertically transmit to the offspring. The neonatal microbiota will affect the newborn’s physiology and future health. Initial colonisation and body site-specific differentiation of the neonatal microbiota may have taken place before birth. (2018): http://gut.bmj.com/content/early/2018/05/14/gutjnl-2018-315988

Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice (Dec 2019, 73 mother-infant dyads) https://www.gutmicrobiotaforhealth.com/an-altered-gut-microbiota-in-mothers-with-ibd-can-be-transferred-to-their-offspring-and-involves-changes-in-mucosal-adaptive-immune-responses

The maternal gut microbiome is the source of the majority of transmitted strains (2018): https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30317-2

Loss of microbial diversity in the mother appears to be cumulative over succeeding generations (2018): https://web.archive.org/web/20190423130243/https://www.mdedge.com/ccjm/article/189671/infectious-diseases/our-missing-microbes-short-term-antibiotic-courses-have-long

Prenatal stress alters gut bacteria to cause lifelong problems in offspring [1][2][3].

Immunology: Mum’s microbes boost baby’s immunity [1].

Microbiota control of maternal behavior regulates early postnatal growth of offspring (Jan 2021, mice) https://advances.sciencemag.org/content/7/5/eabe6563

Early-life exercise may promote lasting brain and metabolic health through gut bacterial metabolites[1][2].

Gestational age, mode of birth and breastmilk feeding all influence acute early childhood gastroenteritis: a record-linkage cohort study [1].

Newborn Gut Bacteria Differs If Infants Breastfed Or Formula-Fed, Vaginal Or Cesarean Birthed [1][2].

Premature birth risk linked to bacteria in vagina and cervix [1][2][3][4]. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes (2018) [1].

It is currently unknown whether the womb is sterile or not [1]. It seems that the presence of bacteria are associated with detrimental outcomes. But even if it is sterile microbial metabolites and stimulation/interaction with the immune system still impact fetal development, and various things like mother's health/microbiome and antibiotics given to the mother during pregnancy/breastfeeding significantly impact the baby's microbiome [1][2][3][4][5].

"breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age (6–9 years of age). Our work highlights the persistent effects of breastfeeding duration and pre-school dietary lifestyle". Impact of early events and lifestyle on the gut microbiota and metabolic phenotypes in young school-age children (2019): https://doi.org/10.1186/s40168-018-0608-z

Early life gut microbiota is associated with rapid infant growth in Hispanics from Southern California (Aug 2021, n=132) https://www.tandfonline.com/doi/full/10.1080/19490976.2021.1961203

Brain function:

Autism Risk Determined by Health of Mom’s Gut, UVA Research Reveals. Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism (2018): https://news.virginia.edu/content/autism-risk-determined-health-moms-gut-uva-research-reveals - http://www.jimmunol.org/content/early/2018/06/29/jimmunol.1701755

Research finds potential mechanism linking autism, intestinal inflammation https://medicalxpress.com/news/2021-12-potential-mechanism-linking-autism-intestinal.html Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells (Dec 2021, mice)

UNC researchers link gut bacteria to infant brain development (2017) [1, 2].

Association of the Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes (Mar 2019) https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2728623 "These epidemiologic findings appear to support the hypothesis that early life gut microbiota are associated with neurodevelopmental outcomes in childhood"

The maternal microbiome modulates fetal neurodevelopment in mice (Sep 2020) https://www.nature.com/articles/s41586-020-2745-3

Virginia Tech scientists find link between microorganisms, early brain development (Dec 2021) https://augustafreepress.com/virginia-tech-scientists-find-link-between-microorganisms-early-brain-development/ Early Influences of Microbiota on White Matter Development in Germ-Free Piglets.

Allergy & asthma:

Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood [1].

Newborn Gut Microbiome Predicts Later Allergy and Asthma [1].

Association Between Use of Multiple Classes of Antibiotic in Infancy and Allergic Disease in Childhood (Dec 2019, n=798,426) https://www.cnn.com/2019/12/20/health/antibiotics-allergies-children-study/index.html "all commonly prescribed antibiotics during infancy are associated with subsequent diagnosis of allergic disease. The risk was lowest for sulfonamides and highest for penicillin"

See also:

https://humanmicrobiome.info/intro#allergy

https://humanmicrobiome.info/probiotics#allergies

Antibiotics:

Analytical approach to antibiotics.

This section covers the lasting, long-term detriments, especially during early life and pregnancy.

More at: https://humanmicrobiome.info/antibiotics

Review, 2018: Antibiotics in early life: dysbiosis and the damage done: https://doi.org/10.1093/femsre/fuy018

"A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice" (Jan 2021, n=98) https://www.nature.com/articles/s41598-021-80982-6 - The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 hours after birth. These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development. Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants.

Antibiotic exposure prevents acquisition of beneficial metabolic functions in the preterm infant gut microbiome (Jul 2022, n=68) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01300-4 "Our findings may provide a mechanistic explanation for the known associations between antibiotic use and adverse outcomes in preterm infants"

Single Course of Antibiotics Early in Life May Increase Type 1 Diabetes Risk (2018): https://www.genengnews.com/topics/omics/single-course-of-antibiotics-early-in-life-may-increase-type-1-diabetes-risk/ - https://doi.org/10.7554/eLife.37816

Maternal antimicrobial use at delivery has a stronger impact than mode of delivery on bifidobacterial colonization in infants: a pilot study (2018): https://www.nature.com/articles/s41372-018-0172-1

"Our results suggest that infants inherit the legacy of past antibiotic consumption of their mothers via transmission of genes" Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements (2018): https://doi.org/10.1038/s41467-018-06393-w

Association Between Use of Multiple Classes of Antibiotic in Infancy and Allergic Disease in Childhood (Dec 2019, n=798,426) https://www.cnn.com/2019/12/20/health/antibiotics-allergies-children-study/index.html "all commonly prescribed antibiotics during infancy are associated with subsequent diagnosis of allergic disease. The risk was lowest for sulfonamides and highest for penicillin"

Antibiotics administered to mothers during childbirth linked to autoimmune diseases in children (Feb 2024, n=45,575) Risk of Immune-related Diseases in Childhood after Intrapartum Antibiotic Exposure. https://medicalxpress.com/news/2024-02-antibiotics-mothers-childbirth-linked-autoimmune.html "This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future."

Early Antibiotic Exposure Linked To Lifelong Asthma And Allergies In Mice (Jul 2022) https://www.iflscience.com/early-antibiotic-exposure-linked-to-lifelong-asthma-and-allergies-in-mice-64675 Influence of the early-life gut microbiota on the immune responses to an inhaled allergen.

Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization (Jan 2021, n=12,422) https://medicalxpress.com/news/2021-01-neonatal-antibiotic-growth-boys.html

Early life exposure to antibiotics in utero and through mother’s milk disrupts beneficial gut bacteria, compromising T-cell development (Feb 2021, mice) https://www.rutgers.edu/news/infant-antibiotic-exposure-can-affect-future-immune-responses-toward-allergies "early-life acquisition of a dysbiotic microbiota has detrimental effects [..] that persist into adulthood" An Antibiotic-Impacted Microbiota Compromises the Development of Colonic Regulatory T Cells and Predisposes to Dysregulated Immune Responses.

"short-term disruption of gut bacteria makes infant mice more likely to develop pneumonia. It also makes them more likely to die from it. Longer term, continued disruptions to gut bacteria appears to cause permanent immune system damage" https://scienceblog.cincinnatichildrens.org/excessive-antibiotic-use-in-newborns-can-permanently-damage-lungs-defenses-study-raises-questions-about-how-antibiotics-are-prescribed/ Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection (2017). The author also criticizes the current antibiotics for GBS practices.

Duplicated in newborn rhesus macaques, and suggests FMT can be a useful intervention (2022) https://www.science.org/doi/10.1126/scitranslmed.abl3981 The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota. "Fecal microbiota transfer was associated with partial correction of the broad immune maladaptations and protection against severe pneumonia"

Antibiotics given in infancy may have adverse impact on adult gut health (Sep 2022, mice) https://medicalxpress.com/news/2022-09-antibiotics-infancy-adverse-impact-adult.html Neonatal antibiotics have long term sex-dependent effects on the enteric nervous system

Antibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections (2018): https://doi.org/10.1093/ije/dyx272

Implications of intrapartum azithromycin on neonatal microbiota. (2017): https://archive.is/4L6Tj "Infant gut microbiota differed significantly with intrapartum antibiotic prophylaxis exposure", "antibiotic-induced alteration of physiological gut microflora has been shown to last into adulthood".

30% overall increased risk for asthma in children of the mothers who used antibiotics (2014): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487629/

Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis (2015): https://www.nature.com/articles/ncomms9424

Any antibiotic exposure was associated with an increased rate of developing juvenile idiopathic arthritis (2015): http://pediatrics.aappublications.org/content/136/2/e333

Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces (2015): http://mbio.asm.org/content/6/6/e01693-15.full

Antibiotic use in preschoolers alters intestinal microbiome, increases disease risk (2016): https://www.healio.com/pediatrics/gastrointestinal-conditions/news/online/%7Bc60c2b80-b4df-4f60-9ae0-e5e01a0f7356%7D/antibiotic-use-in-preschoolers-alters-intestinal-microbiome-increases-disease-risk - Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children https://www.nature.com/articles/ncomms10410

Microbiome: Antibiotics and the infant microflora. Functional selection of novel antibiotic resistance genes and metagenomic sequencing reveal how antibiotic treatment and bacterial resistance genes interact to shape the fragile microbiome of premature infants. (2016): https://www.nature.com/articles/nmicrobiol201640

Impact of Prematurity and Perinatal Antibiotics on the Developing Intestinal Microbiota: A Functional Inference Study (2016): http://www.mdpi.com/1422-0067/17/5/649/htm

Antibiotics, gut bugs and the young. Two recent studies have investigated the effects of antibiotic use on the intestinal microbiota of preterm infants and young children. (2016): https://www.nature.com/articles/nrmicro.2016.73

Pediatric antibiotic administration can have long-term effects on child development (2015): https://biotechin.asia/2015/09/08/pediatric-antibiotic-administration-can-have-long-term-effects-on-child-development/

"Those who had received antibiotics had more behavioural difficulties and more symptoms of depression at follow‐up" https://onlinelibrary.wiley.com/doi/abs/10.1111/apa.13613 Antibiotics in the first year of life and subsequent neurocognitive outcomes (2016).

"early-life exposure to an antibiotic-perturbed low-diversity microbiota is sufficient to cause changes in body weight persisting into adulthood" https://doi.org/10.1038/s42003-018-0140-5 Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups (2018).

Impact of antibiotic treatment on infant gut microbiome revealed. Antibiotic treatment reduces stability, diversity of microbial population in the first 3 years of life (2016): https://www.sciencedaily.com/releases/2016/06/160615151708.htm - Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability http://dx.doi.org/10.1126/scitranslmed.aad0917

Perinatal exposure to tetracycline contributes to lasting developmental effects on offspring (May 2021, mice) https://animalmicrobiome.biomedcentral.com/articles/10.1186/s42523-021-00099-z

Early life antibiotic use enhances the pathogenicity of CD4+ T cells during intestinal inflammation (2016): https://jlb.onlinelibrary.wiley.com/doi/abs/10.1189/jlb.3MA0716-334RR

Early-life Antibiotic Use Disrupts Gut Microbiota and Immune System, MS Rat Study Finds. Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats (Jan 2019) https://multiplesclerosisnewstoday.com/2019/02/13/early-life-antibiotic-use-disrupts-gut-microbiota-ms-rat-study/ - https://www.nature.com/articles/s41598-018-37505-7

A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult (Mar 2019, mice) https://web.archive.org/web/20191112120609/https://old.reddit.com/r/HumanMicrobiome/comments/b3gh0k/a_weaning_reaction_to_microbiota_is_required_for/ "Once the microbiota is destroyed by antibiotics, the immune reaction no longer occurs"

Perinatal antibiotics alter preterm infant EEG and neurobehavior in the Family Nurture Intervention trial (2019): https://doi.org/10.1002/dev.21820 "study examines the effects of perinatal antibiotic exposure on neonatal EEG and attention deficits as measured by the Child Behavior Checklist in 4‐ to 5‐year‐old children who were enrolled in an NICU‐based randomized controlled trial comparing Family Nurture Intervention (FNI) to standard care"

Specific class (penicillins, cephalosporins) of intrapartum antibiotics relates to maturation of the infant gut microbiota: a prospective cohort study (Apr 2019): https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/1471-0528.15799 "findings suggest that intrapartum antibiotics alters the developmental trajectory of the infant gut microbiome, and specific antibiotic types may impact community composition, diversity, and keystone immune training taxa"

Antibiotics in early life slows digestive nerve function, alters microbiome (May 2020, mice) https://medicalxpress.com/news/2020-07-antibiotics-early-life-digestive-nerve.html Antibiotic exposure postweaning disrupts the neurochemistry and function of enteric neurons mediating colonic motor activity.

Amoxicillin Use During Infancy May Be Linked To Tooth Enamel Defects https://www.sciencedaily.com/releases/2005/10/051007094657.htm "increased risk of fluorosis for amoxicillin use from 20-24 months after controlling for otitis media, breast-feeding, and fluoride intake" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556648/

Antibiotics May Blunt Breast-Feeding's Benefits:

Infants given the drugs were prone to infections and obesity in childhood, researchers say (2016): https://www.webmd.com/children/news/20160613/antibiotics-may-blunt-breast-feedings-benefits#1

"Even one day of antibiotics was associated with profound changes in the microbiota of breast milk [..] prolonged effects on the diversity and abundance" (Sep 2020, n=86) https://www.eurekalert.org/pub_releases/2020-09/uot-aab090320.php

Stop the growth of new brain cells:

Antibiotics strong enough to kill off gut bacteria can also stop the growth of new brain cells in the hippocampus, a section of the brain associated with memory, reports a new study in mice. Researchers also uncovered a clue to why -- a type of white blood cell seems to act as a communicator between the brain, the immune system, and the gut. (2016): https://www.sciencedaily.com/releases/2016/05/160519130105.htm - Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis http://dx.doi.org/10.1016/j.celrep.2016.04.074

Cause weight gain:

84% increased risk of obesity at 7 years of age if the mother received antibiotics in second or third trimester of pregnancy (2014): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487629/ - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390478/

Early Life Antibiotic Exposure and Weight Development in Children (2016): https://www.jpeds.com/article/S0022-3476%2816%2930375-4/fulltext

Children Who Take Antibiotics Gain Weight Faster Than Kids Who Don’t. And is also clearly documented in feed animals: https://archive.is/pqE1t - https://www.jhsph.edu/news/news-releases/2015/children-who-take-antibiotics-gain-weight-faster-than-kids-who-dont.t.html - Antibiotic use and childhood body mass index trajectory https://www.nature.com/articles/ijo2015218

Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use (2017): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0245-y

Testosterone disruptor effect and gut microbiome perturbation in mice: Early life exposure to doxycycline (Jan 2019): https://www.sciencedirect.com/science/article/pii/S0045653519301110 "Early-life exposure to low-dose of doxycycline associates with increased risk of obesity."

Associated with subsequent development of Necrotising enterocolitis (NEC), a significant cause of infant morbidity and mortality:

Does antibiotic choice for the treatment of suspected late-onset sepsis in premature infants determine the risk of developing necrotising enterocolitis? A systematic review (2018): https://www.sciencedirect.com/science/article/pii/S0378378218302123

Stool from infants with NEC triggers NEC in mice, proving it's the gut microbiome at cause (2018): https://www.hopkinsmedicine.org/news/newsroom/news-releases/in-mice-johns-hopkins-researchers-find-the-cause-of-and-cure-for-brain-injury-associated-with-gut-condition-in-preemies - http://dx.doi.org/10.1126/scitranslmed.aan0237

Transient neonatal antibiotic exposure increases susceptibility to late-onset sepsis driven by microbiota-dependent suppression of type 3 innate lymphoid cells (Jul 2020, mice) https://www.nature.com/articles/s41598-020-69797-z

Antibiotic exposure was found to be independently predictive of postpartum depressive symptoms at 1‐month and 2‐months postpartum after controlling for baseline predictors:

Maternal peripartum antibiotic exposure and the risk of postpartum depression (2018): https://onlinelibrary.wiley.com/doi/full/10.1002/nur.21881

Breastfeeding:

Review, 2018: Human Breast Milk Bacteriome in Health and Disease https://www.mdpi.com/2072-6643/10/11/1643/htm

Review, 2019: "Variations in human milk (HM) immune and microbial composition may in part explain the controversies that are evidenced in studies that aim to evaluate the prevalence of allergy by prolonged and exclusive breastfeeding" https://academic.oup.com/nutritionreviews/advance-article-abstract/doi/10.1093/nutrit/nuz019/5492496 Reviewing the evidence on breast milk composition and immunological outcomes.

Review, 2021: "maternal health status and diet, gestational age, infant gender, mode of delivery, lactation stage, mode of feeding, geographic location and social network density influence the composition of the human milk microbiota" https://www.sciencedirect.com/science/article/pii/S014600052100121X Factors influencing the microbial composition of human milk.

Research reveals new insight into why breastfed babies have improved immune systems. A specific type of immune cell - called regulatory T cells - expand in the first three weeks of life in breastfed human babies and are nearly twice as abundant as in formula fed babies. These cells also control the baby’s immune response against maternal cells transferred with breastmilk and help reduce inflammation. Moreover, specific bacteria, called Veillonella and Gemella, which support the function of regulatory T cells, are more abundant in the gut of breastfed babies. https://www.birmingham.ac.uk/news/latest/2021/01/breastfed-babies-immune-systems-formula.aspx Breastfeeding promotes early neonatal regulatory T cell expansion and immune tolerance of non‐inherited maternal antigens (Jan 2021).

Breastfeeding, compared with formula feeding, was independently associated with infant intestinal microbial diversity. Breastfeeding also had the most consistent associations with individual taxa that have been previously linked to early-life diet and health outcomes (eg, Bifidobacterium). Maternal diet during pregnancy and solid food introduction were less associated with the infant gut microbiome than breastfeeding status. We found evidence of a possible interaction between breastfeeding and child race/ethnicity on microbial composition. https://doi.org/10.1016/j.jpeds.2018.07.066 Diet during Pregnancy and Infancy and the Infant Intestinal Microbiome (2018).

Breastmilk’s IgA antibody Protects Preemies from Deadly Disease (NEC). Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants (June 2019) https://www.genengnews.com/news/breastmilks-iga-protects-premature-babies-from-deadly-disease/

Gut Bacteria from Breastfeeding Linked to Improved Infant Response to Vaccines (June 2019) https://www.ars.usda.gov/news-events/news/research-news/2019/gut-bacteria-from-breastfeeding-linked-to-improved-infant-response-to-vaccines/

"Fecal microbiota in the neonatal period of preterm infants fed with exclusive own mother’s milk presented increased richness and differences in microbial composition from those fed with different proportions of formula." https://doi.org/10.1371/journal.pone.0217296. Influence of own mother's milk and different proportions of formula on intestinal microbiota of very preterm newborns (May 2019).

Microbiota associated with breastfed babies show health benefits, among other factors [1][2].

Breast milk contains non-digestible oligosaccharides (HMOs - human milk oligosaccharides) that bacteria like b.infantis feed on [1][2]. And these HMOs impact which microbes adhere to the infant gut [1], and thus shape intestinal barrier function [1]. Complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections [1].

Over 1200 genes are differentially regulated between breastfed and formula fed infants [1].

"The absence of breastfeeding may impart lasting effects on the gut microbiome well into childhood" (Jul 2020, adoption-sibling design, n=73) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235223 History of breastfeeding but not mode of delivery shapes the gut microbiome in childhood.

One month after birth, infants receiving Bovine Formula exhibited higher levels of inflammation compared to Breast Milk [1].

Breast milk, formula, the microbiome and overweight (2018): https://www.nature.com/articles/s41574-018-0066-5 Jessica D. Forbes and colleagues found that infants who received formula early in life were more likely to be overweight at 1 year of age than those exclusively breastfed. Formula feeding was associated with altered intestinal microbiome characteristics at 3 months. These findings link early-life formula feeding and an altered microbiome with subsequent overweight.

Human lactoferrin was significantly more effective at inhibiting bacterial growth, when compared to bovine lactoferrin. Effects of lactoferrin on neonatal pathogens and Bifidobacterium breve in human breast milk (2018): https://doi.org/10.1371/journal.pone.0201819

Non-exclusive breastfeeding alters the gut microbiota, increasing T cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced postnatal HIV transmission observed in exclusive-breastfed infants (2018): https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciy265/4961341

Breastfeeding increases microbial community resilience. "results suggested an intestinal microbiota pattern resilient to external forces, due to the probiotic and prebiotic effects of exclusive breastfeeding" (2018): https://www.sciencedirect.com/science/article/pii/S0021755716302923

Study of human milk functional activity vs actual breastfeeding (latching). Infants unable to actively suck were fed mother's milk. Feeding directly from the breast can contribute to the preterm infant’s microbiome assembly, in addition to the intrinsic health-promoting effects of milk itself. The milk microbiome composition seemed to change following the infant’s latching to the mother’s breast, shifting toward a more diverse microbial community https://doi.org/10.3389/fmicb.2018.02512. Microbial Community Dynamics in Mother’s Milk and Infant’s Mouth and Gut in Moderately Preterm Infants (2018). Additional supporting studies.

The process of pumping, storing and bottle-feeding breast milk may reduce the transfer of bacteria from mom to baby https://news.ubc.ca/2020/07/10/mom-and-baby-share-good-bacteria-through-breast-milk/ Breastmilk Feeding Practices Are Associated with the Co-Occurrence of Bacteria in Mothers’ Milk and the Infant Gut: the CHILD Cohort Study (Jul 2020).

Breast milk from unhealthy mothers is bad/worse/unhealthy: https://doi.org/10.1093/ecco-jcc/jjy186 "The profile of human milk metabolome, cytokines and antibodies in inflammatory bowel diseases versus healthy mothers and potential impact on the newborn (2018)"

Review shows that donor milk does not promote the growth and development of preterm infants as well as maternal milk (Review, Dec 2018): https://onlinelibrary.wiley.com/doi/abs/10.1111/apa.14702 "Many of the components in raw maternal breast milk were lacking in pasteurised donor milk, which was inferior in promoting the growth and development of very preterm infants"

Breastmilk sugars, long believed to be fixed in their composition, differ in pregnant women on probiotics (L GG, L LC705, B Bb99, P shermanii JS). Association of Maternal Probiotic Supplementation With Human Milk Oligosaccharide Composition (Jan 2019). https://www.urmc.rochester.edu/news/story/breastmilk-sugars-differ-in-pregnant-women-on-probiotics

C-section vs Vaginal birth:

Time to consider the risks of caesarean delivery for long term child health (2015): https://doi.org/10.1136/bmj.h2410

Opinion, Sep 2022: Crucial nuances in understanding (mis)associations between the neonatal microbiome and Cesarean delivery https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(22)00185-X

Review, 2018: Dysbiosis in Children Born by Caesarean Section https://www.karger.com/Article/FullText/492168 "Microbial dysbiosis caused by Caesarean-section delivery has been associated with an increased risk of conditions such as asthma, obesity, food allergies, type 1 diabetes (T1D), systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease (IBD), and leukemia."

Vaginal seeding: Swabbing cesarean-born babies with vaginal fluids potentially unsafe and unnecessary. "this difference is most likely caused by antibiotics administered to mothers delivering by C-section rather than not being exposure to vaginal microbes". https://medicalxpress.com/news/2018-05-swabbing-cesarean-born-babies-vaginal-fluids.html | A Critical Review of the Bacterial Baptism Hypothesis and the Impact of Cesarean Delivery on the Infant Microbiome (Review, 2018): https://www.frontiersin.org/articles/10.3389/fmed.2018.00135/full

Maternal vaginal microbiome composition does not affect development of the infant gut microbiome in early life (Mar 2023, n=621) https://blog.frontiersin.org/2023/03/30/maternal-vaginal-microbiome-composition-influence-baby/ "Antibiotic use may explain microbiome discrepancies"

"The study authors also genetically sequenced the gut microbiomes of 175 mothers in addition to their babies and learned that the vaginally born infants’ guts were not determined by bacteria found in the vaginal canal they encountered during birth. The finding calls into question the controversial practice of vaginal swabbing or “seeding”. “There’s no evidence that it works,” says David Eschenbach, professor of obstetrics and gynecology at the University of Washington School of Medicine" (Sep 2019) https://archive.fo/v6wHA#selection-799.0-799.1

"we assess the effect of delivery mode on gut microbiota, independent of intrapartum antibiotics, by postponing routine antibiotic administration to mothers. This difference seemed independent of the IV antibiotics administered to the mothers" https://archive.ph/t7EaR Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life (Nov 2019, 120 children) "Perhaps therefore not solely vaginal microbiota seeding but also fecal microbiota seeding during vaginal delivery is instrumental in shaping the newborn’s gut microbial environment"

Another 2021 study concluding the c-section itself is the cause, rather than the antibiotics: https://gut.bmj.com/content/early/2021/11/18/gutjnl-2021-324767 Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial (Nov 2021, n=63) "Profound differences were found in microbial diversity and composition in both CS groups in the first month of life. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome."

Beneficial bacteria can be restored to C-section babies at birth (Jun 2021, n=177) https://archive.ph/4vrGo Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.

Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial (Jun 2021, n=47) https://www.sciencedirect.com/science/article/pii/S235239642100236X "no observed differences in gut microbiome composition or functional potential at 1 mo or 3 mo of age"

Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study (Oct 2020, n=7) https://archive.ph/OHfoK "our findings warn against unsupervised, parent-driven maternal microbiota transfer (vaginal or fecal) to neonates because the probability of transmitting harmful microbes appears to be high" - "vaginal swabbing does not correct the CS-induced microbiota imbalance"

Vaginal microbiota seeding improves the neurodevelopment of babies born via C-section, reveals triple-blind trial (Jun 2023, n=68) https://medicalxpress.com/news/2023-06-vaginal-microbiota-seeding-neurodevelopment-babies.html Effects of vaginal microbiota transfer on the neurodevelopment and microbiome of cesarean-born infants: A blinded randomized controlled trial.

C-section babies have a higher risk of developing a variety of chronic illness vs children born vaginally [1]. In 2016 it seemed to be due to health problems in the mother which also caused the c-section, rather than the c-section itself causing problems with the child [1]. In 2018 (see above) it's said to be from the antibiotics. In 2019 a study controlled for intrapartum antibiotics and still found that c-section infants had different microbes, and those differences were not able to be overcome by breastfeeding [1].

Editorial, 2018: Caesarean-Section and Neonatal Gut Microbiome: Short and Long Term Effects and New Targets for Early Prevention: https://www.karger.com/Article/FullText/491812

Review, 2018: C-section and the Neonatal Gut Microbiome Acquisition: Consequences for Future Health: https://www.karger.com/Article/FullText/490843

Review, 2018: Birth Mode-Related Differences in Gut Microbiota Colonization and Immune System Development: https://www.karger.com/Article/FullText/490842 "Given that the first months of life represent a crucial time window in the ontogenesis of the immune system and the establishment of tolerance, C-section delivery will impact on the lifelong risk of developing immune disease."

Delivery mode and gut microbial changes correlate with an increased risk of childhood asthma (Nov 2020, n=700) https://stm.sciencemag.org/content/12/569/eaax9929 - https://www.eurekalert.org/pub_releases/2020-11/uoc-roc111220.php

Non-elective vs elective c-sections affect the bacterial composition of breast milk [1]. Contradicted by newer study (2016).

Birth mode results in distinctly different infant gut virome/phageome communities, with spontaneous vaginal delivery (SVD) infants having greater viral and bacteriophage diversity (2018): https://peerj.com/articles/4694/

Cesarean delivery is associated with decreased beneficial gut microbes and increased pathobionts and butyrate excretion: a longitudinal study over the first year of life (Dec 2020, n=70) https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.16633

Altered microbiome after caesarean section impacts baby's immune system (2018): https://www.sciencedaily.com/releases/2018/11/181130094328.htm

Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential (2018): https://www.nature.com/articles/s41467-018-07631-x "c-section disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune-stimulatory potential during a critical window for neonatal immune system priming"

Women who have C-sections are no more likely to have children who develop obesity than women who give birth naturally, according to a large study by researchers at Karolinska Institutet in Sweden. The findings contradict several smaller studies that did find an association, but did not consider the numerous maternal and prenatal factors that the researchers did in this study. The strongest confounder in the association between mode of delivery and obesity was how much the mother weighed before she became pregnant. This is consistent with previous reports on the heritability of obesity and the influence of maternal obesity on fetal health. (Dec 2019) https://news.ki.se/study-debunks-notion-that-c-section-would-increase-risk-of-obesity-in-the-child

Contradictory April 2020 study of 33,226 women born by cesarean section found they were 11% more likely to be obese and had a 46% higher chance of developing type 2 diabetes (T2D) compared with women born by vaginal delivery https://www.news-medical.net/news/20200413/Women-born-by-cesarean-have-greater-risk-of-obesity-and-diabetes.aspx Association of Birth by Cesarean Delivery With Obesity and Type 2 Diabetes Among Adult Women.

Diet:

Maternal diet alters the breast milk microbiome and microbial gene content [1], oligosaccharide composition [1], breast microbiome [1], and influences the child's food allergy risk [1].

Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner (2018): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0490-8

Mom's Diet Right Before Pregnancy Can Alter Baby's Genes: http://www.npr.org/sections/health-shots/2014/04/29/307787984/moms-diet-right-before-pregnancy-can-alter-babys-genes

Maternal fiber deprivation alters microbiota in offspring, resulting in low-grade inflammation and predisposition to obesity (Dec 2022, mice) https://www.eurekalert.org/news-releases/972806

Pregnant women who fast for Ramadan risk damage to their babies[1][2][3].

Diet plays important role in determining vaginal microbiome [1].

Solid foods take over shaping the gut after 9 months [1], and early childhood diet influences food allergy risk [1].

Study finds childhood diet has lifelong impact (Jan 2021, mice) https://www.eurekalert.org/pub_releases/2021-02/uoc--sfc020221.php

Critical Windows for the Programming Effects of Early-Life Nutrition on Skeletal Muscle Mass (2018): https://www.karger.com/Article/FullText/486490

Stunting is a largely irreversible outcome of inadequate nutrition (maternal and infant/child) and repeated bouts of infection during the first 1000 days of a child’s life. Stunting has long term effects on individuals and societies, including: diminished cognitive and physical development, reduced productive capacity and poor health, and an increased risk of degenerative diseases such as diabetes. http://www.who.int/nutrition/topics/globaltargets_stunting_policybrief.pdf - http://www.who.int/nutrition/healthygrowthproj_stunted_videos/en/

Review, 2018: Epigenetic Mechanisms Link Maternal Diets and Gut Microbiome to Obesity in the Offspring: https://doi.org/10.3389/fgene.2018.00342

GBS (Group-B Strep):

Current evidence does not support antibiotics for GBS: https://humanmicrobiome.info/antibiotics/#antibiotics-for-gbs-group-b-strep

Waterbirth and GBS (2010) https://pubmed.ncbi.nlm.nih.gov/21322437/ "low-risk women who give birth in water may have a far lower rate of newborn GBS than women who have a dry birth"

Supplementation of Probiotics in Pregnant Women Targeting Group B Streptococcus Colonization: A Systematic Review and Meta-Analysis (2022) https://www.mdpi.com/2072-6643/14/21/4520 "Probiotic administration during pregnancy, namely in the third trimester, was associated with a reduced GBS recto-vaginal colonization at 35–37 weeks and a safe perinatal profile"

Obesity:

BMI of adopted children correlates with the BMI of their biological parents, not their adoptive parents. Shows obesity/BMI is transferred from biological mother [1][2][3].

Maternal obesity has variety of adverse health impacts on child [1].

Maternal obesity increases the risk of hepatocellular carcinoma through the transmission of an altered gut microbiome (Mar 2024, mice) https://www.sciencedirect.com/science/article/pii/S2589555924000570

Maternal pre-pregnancy overweight and neonatal gut bacterial colonization are associated with cognitive development and gut microbiota composition in pre-school-age offspring (Dec 2021, 90 families) https://www.sciencedirect.com/science/article/abs/pii/S0889159121006401

Intestinal microbiome of children born to obese mothers significantly different from those born to mothers of healthy weight [1].

Pediatric obesity is associated with an altered gut microbiota [1].

Diet induced maternal obesity affects offspring gut microbiota and persists into young adulthood (2018): https://doi.org/10.1039/c8fo00444g

Infants born to obese mothers risk developing liver disease, obesity. CU Anschutz researchers find that infant gut microbes altered by maternal obesity may lay foundation for future disease https://www.cuanschutztoday.org/infants-born-to-obese-mothers-risk-developing-liver-disease-obesity. "The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD" (2018): https://www.nature.com/articles/s41467-018-06929-0

Women who have C-sections are no more likely to have children who develop obesity than women who give birth naturally, according to a large study by researchers at Karolinska Institutet in Sweden. The findings contradict several smaller studies that did find an association, but did not consider the numerous maternal and prenatal factors that the researchers did in this study. The strongest confounder in the association between mode of delivery and obesity was how much the mother weighed before she became pregnant. This is consistent with previous reports on the heritability of obesity and the influence of maternal obesity on fetal health. (Dec 2019) https://news.ki.se/study-debunks-notion-that-c-section-would-increase-risk-of-obesity-in-the-child

Contradictory April 2020 study of 33,226 women born by cesarean section found they were 11% more likely to be obese and had a 46% higher chance of developing type 2 diabetes (T2D) compared with women born by vaginal delivery https://www.news-medical.net/news/20200413/Women-born-by-cesarean-have-greater-risk-of-obesity-and-diabetes.aspx Association of Birth by Cesarean Delivery With Obesity and Type 2 Diabetes Among Adult Women.

Probiotics:

FDA Warning Letters Issued to Two Companies for Illegally Selling Probiotic Products to Treat Diseases in Preterm Infants. FDA Raises Concerns About Probiotic Products Sold for Use in Hospitalized Preterm Infants (Oct 26, 2023) https://forum.humanmicrobiome.info/threads/abbott-to-cease-sale-of-infant-probiotic-products-similac-probiotic-tr.190/

Systematic review, Mar 2020: Probiotics for Preterm Infants in India – Systematic Review and Meta-Analysis of Randomized Controlled Trials https://link.springer.com/article/10.1007/s12098-020-03223-0 "We included nine RCTs and a total of 1514 preterm infants. We found a 42% reduction in mortality, 69% reduction in the incidence of definite necrotizing enterocolitis (NEC) and 44% reduction in the rate of late onset sepsis (LOS) in the probiotic group compared to the control group. Significant reduction in the time to full enteral feeds and duration of hospitalization was noted in the probiotic group. Strain selection essential for further research"

Systematic review, Dec 2019: Effect of Probiotic Supplementation in Pregnant Women: A Meta-analysis of Randomized Controlled Trials https://archive.ph/Y2Ovv - some probiotics were helpful for some people/conditions, but not others.

Systematic review, April 2019: Probiotics improve glucose and lipid metabolism in pregnant women: a meta-analysis http://atm.amegroups.com/article/view/24145/23100

Systematic review, Oct 2018: Effect of prebiotic and probiotic supplementation on neurodevelopment in preterm very low birth weight infants: findings from a meta-analysis (2018): https://www.nature.com/articles/s41390-018-0211-9 - Limited evidence from RCTs does not demonstrate a difference in neurodevelopmental outcomes between prebiotic/probiotic treated and untreated control groups

Systematic Review, Cochrane, 2018: Maternal probiotic supplementation for prevention of morbidity and mortality in preterm infants https://doi.org/10.1002/14651858.CD012519.pub2 "insufficient evidence"

Review, Feb 2019: "clinical results on the effects of probiotics on low birth weight (LBW) infant growth are either inconsistent or contradictory with each other" https://doi.org/10.1080/1040841X.2018.1561643

Benefits:

Review, Mar 2024: Probiotics supplementation during pregnancy or infancy on multiple food allergies and gut microbiota: a systematic review and meta-analysis https://academic.oup.com/nutritionreviews/advance-article/doi/10.1093/nutrit/nuae024/7631797 "Probiotics supplementation during pregnancy and infancy reduced the risk of total food allergy, cow-milk allergy, and egg allergy. Infancy-only supplementation lowered cow-milk allergy risk, while pregnancy-only had no discernible effect. Benefits were observed with over 2 probiotic species, and a daily increase of 1.8 × 109 colony-forming units during pregnancy and infancy correlated with a 4% reduction in food allergy risk."

Probiotics added to maternal nutrition affect ınfantile colic symptoms and fecal microbiota profile: a single-blind randomized controlled study (Sep 2022, n=31) https://e-cep.org/journal/view.php?doi=10.3345/cep.2022.00766 "Infants whose mothers were supplemented with Actiregularis for 15 days showed a decreased frequency and intensity of crying as well as a significantly increased bacterial diversity in the stools"

Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants (May 2022, n=57) https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(22)00211-6

Administration of Infloran (Bifidobacterium bifidum BB07 and Lactobacillus acidophilus LA37), associated with a significantly decreased risk of NEC and late-onset sepsis in our neonatal unit, and no safety issues. https://medicalxpress.com/news/2019-11-billions-bacteria-boost-gut-health.html. Incidence of necrotising enterocolitis before and after introducing routine prophylactic Lactobacillus and Bifidobacterium probiotics (Oct 2019).

Two probiotic mixtures of bifidobacteria and lactobacilli reduce incidence of NEC in preterm neonates (Oct 2020, n=80) https://www.tandfonline.com/doi/full/10.1080/19490976.2020.1826747 Influence of probiotic supplementation on the developing microbiota in human preterm neonates.

Babies who took a L. plantarum ATCC-202195 + FOS synbiotic concoction had a significantly lower risk of developing sepsis—a life-threatening condition where infections trigger body-wide inflammation (2017): https://archive.fo/oJvvP

Probiotic gives long-standing protection against childhood eczema, study finds. https://medicalxpress.com/news/2018-12-probiotic-long-standing-childhood-eczema.html - Effects of Lactobacillus rhamnosus HN001 in early life on the cumulative prevalence of allergic disease to 11 years (2018): https://doi.org/10.1111/pai.12982

Harms:

After death of infant, FDA warns hospitals about probiotics for premature babies (Oct 2023) Evivo with MCT Oil, Infinant Health, Bifidobacterium longum subsp. infantis EVC001. https://forum.humanmicrobiome.info/threads/after-death-of-infant-fda-warns-hospitals-about-probiotics-for-prematu.172/

Mothers self-administering probiotics during breastfeeding, as well as directly to their infants, with either random/general probiotics, or BioGaia, resulted in poorer health outcomes and suggests that probiotic exposure during infancy has limited effects on gut microbial composition yet is associated with increased infection later in life. (2018): https://www.nature.com/articles/s41598-018-26423-3

As density of L. reuteri DSM 17938 (BioGaia) was associated with increased crying time, L. reuteri supplementation may not be an appropriate treatment for all infants with colic. https://www.nature.com/articles/s41598-017-15404-7

A new risk factor for neonatal vancomycin-resistant Enterococcus colonisation: bacterial probiotics (Sep 2014, n=210) https://www.tandfonline.com/doi/abs/10.3109/14767058.2014.958462 "Probiotic and vancomycin exposure were significant risk factors for VRE colonisation. The acquisition and transfer of resistance genes of bacteria may be mediated by probiotics. Therefore, the safety of probiotics is a concern and should be investigated further"

Lactobacillus Sepsis following a Laparotomy in a Preterm Infant: A Note of Caution (Mar 2016) https://www.karger.com/Article/Abstract/441965

Misc:

The recommendations for neonates are essentially the same as adults (2011): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163616/

See probiotic guide for more: https://humanmicrobiome.info/probiotic-guide and https://humanmicrobiome.info/probiotics

In my opinion the current evidence suggests that general/random probiotic usage isn't generally beneficial. It greatly matters which probiotic you take and how your body responds to it. Even for the study showing benefits against sepsis, that specific synbiotic is unlikely to be a universal good.

Vaginal Microbiome:

Diet plays important role in determining vaginal microbiome [1].

Premature birth risk linked to bacteria in vagina and cervix [1][2][3][4][5][6].

Vaginal dysbiosis in pregnancy associates with risk of emergency caesarean section: a prospective cohort study (Sep 2021, n=738) https://science.ku.dk/english/press/news/2021/widespread-vaginal-condition-could-lead-to-emergency-caesarean-section/

The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model (Nov 2021) https://www.sciencedaily.com/releases/2022/01/220127104217.htm

Heritable vaginal bacteria influence immune tolerance and relate to early-life markers of allergic sensitization in infancy (Aug 2022, n=356) https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00256-7

Alteration of vaginal microbiota in patients with unexplained recurrent miscarriage (Mar 2019): https://doi.org/10.3892/etm.2019.7337

Miscarriage may be linked to changes in vaginal bacteria (Jan 2022, n=167) https://www.imperial.ac.uk/news/234036/miscarriage-linked-changes-vaginal-bacteria/ Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation.

The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes (2018) [1].

Vaginal bacterial community composition influences pregnancy outcome (2018): https://doi.org/10.1016/j.trsl.2018.12.005

Review, 2019: The relation of the vaginal microbiota to early pregnancy development during In Vitro Fertilization treatment—A meta-analysis: https://doi.org/10.1016/j.jogoh.2019.01.007 "women with an abnormal vaginal microbiota are roughly 1.4 times less likely to have a successful early pregnancy development after IVF treatment"

Study identifies possible causes of and protectors against premature birth. Seven bacteria and immune factors in the vagina and cervix may be the key to predicting and preventing premature birth https://www.eurekalert.org/pub_releases/2019-03/uoms-bai032119.php. Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery (Mar 2019): https://www.nature.com/articles/s41467-019-09285-9

More at:


Many more can be found via https://microbiomedigest.com/category/pregnancy-and-birth/ use ctrl+f for "Pregnancy and birth".