Claus Thagaard Christophersen

Background: Prebiotics promote growth of beneficial gut bacteria, whereas antibiotics can disrupt the microbial balance, reduce diversity, and potentially cause gut dysbiosis. This investigation aimed to determine whether antibiotic use before, during, or after birth altered the risk of infant allergic disease outcomes within a maternal prebiotic dietary supplementation trial. Methods: Maternal participants were allocated to consume daily prebiotics (galacto‐oligosaccharides and fructo‐oligosaccharides) or placebo (maltodextrin) powder from 18 to 20 weeks' gestation until 6 months postnatal. All infants had a family history of allergic disease. Maternal and infant antibiotic use was prospectively collected monthly throughout the trial intervention period, and infant allergic disease was assessed by 1 year of age. Results: Overall, 83.1% (472/568) mothers and 20.8% (115/554) infants received antibiotics during the trial intervention period. Prebiotic supplementation modified the association between maternal intrapartum antibiotic exposure and infant allergic disease. Among women not consuming prebiotics, maternal intrapartum antibiotics were associated with an increased risk of infant allergen sensitisation (adjusted relative risk [aRR] 3.56, 95% CI 1.65–7.69), IgE‐mediated food allergy (aRR 5.67, 95% CI 2.04–15.73), and medically diagnosed atopic eczema (aRR 6.42, 95% CI 2.43–16.95); such associations were not evident in women consuming prebiotics. Maternal and infant antibiotics administered during other intervention phases were not significantly associated with any infant allergic disease outcomes. Conclusion: Our exploratory investigation findings indicate that maternal prebiotics supplementation reduces the risk of infant allergen sensitisation, food allergy and atopic eczema associated with intrapartum antibiotic use. Future allergy prevention trials could further optimise maternal prebiotic interventions during the intrapartum period.

The Mediterranean diet (MD), known for its high intake of fruits, vegetables, whole grains, legumes, and healthy unsaturated fats, has been linked to a diverse and beneficial gut microbiome. However, its effect on the gut microbiome during pregnancy remains understudied. This study aimed to investigate the impact of high adherence to a Mediterranean diet on gut microbiome composition and function in pregnant women by analysing their metabolic profiles and faecal microbiome composition. Stool, serum, and urine samples were collected from 48 pregnant women at weeks 20/28 and at week 36. Participants were stratified based on MD adherence using a validated questionnaire. Stool samples underwent 16 S rRNA gene amplicon sequencing, and serum short-chain fatty acids (SCFAs) were measured using UPLC-MS. Women with high MD adherence showed significantly higher α-diversity in their faecal microbiomes at both time points. Significant differences in microbiome composition were observed between low and high adherence groups at weeks 20/28, but not at week 36. No significant differences in serum short-chain fatty acid concentrations were found between the groups. Our findings suggest that adherence to the Mediterranean diet during pregnancy is associated with changes in gut microbiome diversity and function. These results contribute to a better understanding of how dietary patterns during pregnancy may influence gut microbiome ecology.

Studies characterising the immunoglobulin (Ig)-bound microbiota apply varying methodologies, making comparisons difficult. This scoping review synthesised evidence on Ig–microbiota binding patterns in maternal and infant contexts, identified recurrent Ig-bound and -unbound bacteria across studies, and highlighted knowledge gaps for further study. Nine articles investigating Ig–microbiota binding patterns in stool or breastmilk samples in mothers or infants were included. Ig–microbiota associations were influenced by sample type, Ig-subclass, genetics, and diet. The most important antibody was IgA, with partial functional redundancy with IgM, while IgG appeared more selective for pathobionts. Ig-bound taxa in early life included important commensals and pathobionts, with high levels of individuality. Ig–microbiota associations shifted with microbiome maturation, environmental and host factors, resembling adults at around 2 years of age. Transfer of Ig-bound Bifidobacterium through breastmilk may contribute to vertical transmission from mother to infant. Ig–microbiota associations also differed between health and disease states, beyond the overall microbiota. Results were limited by study numbers and a lack of methodological consistency. We propose the standardised term “Ig-Seq” in referring to the technique to study Ig–microbiota binding patterns, and suggest standardisation of laboratory protocols, bioinformatic pipelines, and statistical analyses to improve consistency in Ig-Seq.

Background Water chlorination is essential for controlling harmful microbes in drinking water; however, the antimicrobial effects of chlorine-based disinfectants present in tap water may influence early-life gut microbial ecology. Objective To investigate the functional and compositional impact of chlorinated drinking water on the gut microbiome of infants. Design The waTer qUality and Microbiome Study (TUMS) was an Australian-based double-blinded, randomised controlled trial. Six-month-old infants (n = 197) received either de-chlorinated drinking water via benchtop filtration (treatment, n = 99), or regular chlorinated water (control, n = 98) for twelve months. Tap water and stool samples were collected at baseline and at end of intervention. Metagenomic sequencing was used for faecal microbiome analysis. Primary outcomes were differences in gut microbiota between groups, secondary outcomes included incidence of allergic sensitization and respiratory conditions. Results At baseline, 170 stool samples (83 control, 87 intervention) were collected, with 130 samples obtained at the end of the intervention (65 control, 65 intervention). Overall community structure was similar between groups after the intervention, including beta diversity (0.56% variance explained; p = 0.84), richness (−4.25, 95% CI; −14.85 to 6.35, p = 0.43) or Shannon Index (−0.14, 95% CI; −0.32 to 0.04, p = 0.12). The chlorinated water group showed enrichment of antibiotic resistance MetaCyc groups and pathways (adjusted p < 0.05). Stratified analysis suggested this effect was potentiated by clinical antibiotic use. Conclusion Chlorinated drinking water may enhance resistance functions in the infant gut microbiome. While remaining vital for public health, future studies should explore whether adjusting the timing or method of drinking water disinfectants into the infant diet can reduce selective pressures. Trial registration ACTRN12619000458134; https://www.anzctr.org.au

Background: Periodontitis has been epidemiologically associated with adverse pregnancy outcomes, but causality remains difficult to establish in humans due to confounding factors. This study uses a controlled murine model to examine the effects of experimentally induced periodontitis on the composition of the gut microbiota and gastrointestinal inflammation during pregnancy. Methods: Periodontitis was induced in pregnant BALB/c mice via oral inoculation with Porphyromonas gingivalis and Fusobacterium nucleatum before conception ( n = 20 per group). Pregnancy outcomes, gut histology, systemic inflammatory markers, and microbiome composition, assessed by 16S rRNA sequencing, were evaluated at gestational Day 18. Results: Periodontitis was confirmed by significant alveolar bone loss. While fetal and placental weights were modestly increased in periodontitis‐positive mice, there were no changes in implantation rates or placental efficiency. Systemic inflammatory markers, including C‐reactive protein and interleukin‐33, were reduced, suggesting pregnancy‐specific immunomodulation. Histological analysis revealed significant inflammation in the jejunum and colon of periodontitis‐exposed mice. Despite this, alpha and beta diversity metrics of the gut microbiota remained essentially unchanged. Taxonomic shifts were observed at the genus level, with reductions in protective taxa, such as Akkermansia muciniphila and increases in potentially pro‐inflammatory genera, like Desulfovibrio . Conclusions: Periodontitis during pregnancy alters gut microbial composition and increases gastrointestinal inflammation without overtly impairing pregnancy outcomes in mice. These findings suggest an association between oral inflammation, intestinal inflammatory changes, and systemic inflammatory modulation during pregnancy. Further studies are warranted to explore long‐term maternal and offspring consequences and their relevance to human pregnancy. Plain language summary: This study explored how periodontitis during pregnancy can influence the gut and immune system. Periodontitis is already associated with poor pregnancy outcomes, but establishing cause and effect in humans is difficult. To investigate this, the researchers used a controlled mouse model. We induced periodontitis in pregnant mice and examined its impact on the gut microbiome, intestinal health, and immune responses. The results revealed that periodontitis does not stay confined to the mouth; it disrupts gut bacterial balance, causes gut inflammation, and modifies immune pathways. Notably, these effects occurred during pregnancy, a time when the immune system is already adapting. The findings suggest that oral infections during pregnancy can have widespread effects, impacting gut health and immune regulation. This may help explain the link between periodontitis and human pregnancy complications. Overall, the study underscores the importance of oral health during pregnancy and supports the idea that treating periodontitis might also safeguard gut and immune health, leading to better outcomes for both mothers and their babies.

Vaginal microbiome composition has been linked to risk of preterm birth (PTB), a persistent global health challenge. 16S rRNA microbial profiling has identified specific vaginal community state types (CSTs) that have been associated with PTB risk. Diagnostic profiling requires standardised pre-analytical protocols. We evaluated two storage methods and validated a curated, vagina-specific 16S rRNA gene database (VagDB) to enhance annotation. Paired Copan FLOQ swabs from 22 women at high PTB risk were processed for either (a) dry/immediate freezing or (b) Amies-stabilisation/refrigeration. Amplicon sequence variants were generated via 16S rRNA gene (V4) PCR and Illumina sequencing. We assessed diversity, composition, and community state type (CST) allocation. Amies-stabilised samples yielded significantly higher DNA (p = 0.003), but this did not alter species richness, evenness, or community structure. VagDB enhanced species-level resolution. PCoA showed robust clustering by participant and CST (p < 0.001), irrespective of storage; CST concordance exceeded 90%. Routinely collected vaginal swabs in stabilisation medium with an 8–72 h refrigeration window yield reliable data, supporting the integration of vaginal microbiome profiling into clinical PTB risk assessment.

Vaginal microbiome composition has been linked to risk of preterm birth (PTB), a persistent global health challenge. 16S rRNA microbial profiling has identified specific vaginal community state types (CSTs) that have been associated with PTB risk. Diagnostic profiling requires standardised pre-analytical protocols. We evaluated two storage methods and validated a curated, vagina-specific 16S rRNA gene database (VagDB) to enhance annotation. Paired Copan FLOQ swabs from 22 women at high PTB risk were processed for either (a) dry/immediate freezing or (b) Amies-stabilisation/refrigeration. Amplicon sequence variants were generated via 16S rRNA gene (V4) PCR and Illumina sequencing. We assessed diversity, composition, and community state type (CST) allocation. Amies-stabilised samples yielded significantly higher DNA (p = 0.003), but this did not alter species richness, evenness, or community structure. VagDB enhanced species-level resolution. PCoA showed robust clustering by participant and CST (p < 0.001), irrespective of storage; CST concordance exceeded 90%. Routinely collected vaginal swabs in stabilisation medium with an 8–72-hour refrigeration window yields reliable data, supporting the integration of vaginal microbiome profiling into clinical PTB risk assessment.

Complementary feeding induces dramatic ecological shifts in the infant gut microbiota toward more diverse compositions and functional metabolic capacities, with potential implications for immune and metabolic health. The aim of this study was to examine whether the age at which solid foods are introduced differentially affects the microbiota in predominantly breastfed infants compared with predominantly formula-fed infants. We performed whole-genome shotgun metagenomic sequencing of infant stool samples from a cohort of six-month-old Australian infants enrolled in a nested study within the ORIGINS Project longitudinal birth cohort. Infants born preterm or those who had been administered antibiotics since birth were excluded. The taxonomic composition was highly variable among individuals at this age. Predominantly formula-fed infants exhibited a higher microbiome diversity than predominantly breastfed infants. Among the predominantly breastfed infants, the introduction of solid foods prior to five months of age was associated with higher alpha diversity than solid food introduction after six months of age, primarily due to the loss of Bifidobacterium infantis. In contrast, the age at which solid food was introduced was not associated with the overall change in diversity among predominantly formula-fed infants but was associated with compositional changes in Escherichia abundance. Examining the functional capacity of the microbiota in relation to these changes, we found that the introduction of solid foods after six months of age was associated with elevated one-carbon compound metabolic pathways in both breastfed and formula-fed infants, although the specific metabolic sub-pathways differed, likely reflecting different taxonomic compositions. Our findings suggest that the age of commencement of solid foods influences the gut microbiota composition differently in predominantly breastfed infants than in predominantly formula-fed infants.

Diabetes is the leading cause of kidney disease, and as the number of individuals with diabetes increases there is a concomitant increase in the prevalence of diabetic kidney disease (DKD). Diabetes contributes to the development of DKD through a number of pathways, including inflammation, oxidative stress, and the gut-kidney axis, which may be amenable to dietary therapy. Resistant starch (RS) is a dietary fibre that alters the gut microbial consortium, leading to an increase in the microbial production of short chain fatty acids. Evidence from animal and human studies indicate that short chain fatty acids are able to attenuate inflammatory and oxidative stress pathways, which may mitigate the progression of DKD. In this review, we evaluate and summarise the evidence from both preclinical models of DKD and clinical trials that have utilised RS as a dietary therapy to limit the progression of DKD.