Do probiotics have a place in preterm birth?

Unexpected early arrival is never a good thing, no matter how excited you are to meet a new baby. A serious problem around the world is preterm birth (PTB), which happens when a child is born before 37 weeks of pregnancy. The estimated 15 million instances of spontaneous preterm birth (SPTB) per year are the leading cause of infant death under the age of five. Ascending bacterial infections of the uterine cavity, one of the several risk factors for PTB, are responsible for the majority of spontaneous preterm births. Hence, the cervicovaginal microbiome has received greater attention recently.

Many risk factors can have an impact on foetal developmental plasticity, gestational age, or birth outcome even though the pathophysiology of PTB is poorly known.

Toxins, a high-fat diet, a family history of PTB, a lack of education, low socioeconomic status, a short pregnancy interval, an early or late pregnancy (before the age of 16 or after the age of 36), the use of tobacco or alcohol, high stress levels, hypertension, obesity or underweight, an infection, a short cervix, uterine anomalies, and previous miscarriages are some of the environmental and clinical factors included in this list.

The host cervicovaginal microbiota and quantities of produced metabolites can now be added to the list as regulators of the interaction between the maternal and foetal immune systems as well as the outcome of childbirth.

Women of reproductive age often have a cervicovaginal microbiota that is dominated by Lactobacillus species. In contrast, an aberrant microbiota is characterized by an excess of anaerobic bacteria such Mollicutes, Prevotella spp., Gardnerella vaginalis, and Bacteroides spp., as well as a low concentration of lactobacilli. By using a variety of processes, including the creation of lactate and hydrogen peroxide, lactobacilli inhibit the growth of infections, lowering the pH of the vagina.

It is commonly acknowledged that inflammation and intrauterine infection play a significant role in the development of spontaneous PTB, which is assumed to result from pathogen ascent from the vagina.

For instance, a rise in the pathogenic microbiota during the first trimester of pregnancy allows for the metabolic fingerprints of bacterial vaginosis (BV), which is closely associated with the risk of PTB. A reduction in lactobacilli, an increase in pathogens, and the production of pro-inflammatory cytokines are the hallmarks of bacterial vaginosis (BV).

The connection between the cervicovaginal microbiota and spontaneous PTB has been the subject of numerous investigations. Nevertheless, a 2022 analysis of the data revealed that the outcomes vary according to ethnicity. Importantly, one study discovered that Black American women had more species diversity and lactobacilli depletion than white women. Compared to white women, African American women had a higher prevalence of BV-related microbiota. Yet, it’s interesting to note that higher species diversity and a lack of Lactobacillus were regarded as PTB risk factors exclusively in white women, not in African American women.

Here are just a few of the important discoveries made during the review

• In a 2020 study, Lactobacillus crispatus was highly connected with full-term pregnancies, whereas other microbial communities were linked to PTB.
• There were larger concentrations of Lactobacillus crispatus, Lactobacillus gasseri, or Lactobacillus jensenii DNA in the vaginal swabs of an Australian cohort (mainly white women) who went on to deliver at term.
• L. crispatus and L. gasseri were found to play a protective effect in lowering the risk of PTB in a study from India.
• When compared to women who gave birth at term in a different study, the microbiota of women who underwent PTB exhibited higher richness and variety and higher Mollicutes predominance.

The predominance of Lactobacillus spp. in the healthy vaginal tract is well known to support vaginal homeostasis and prevent the colonization and proliferation of harmful microbes.

A number of methods are used by Lactobacillus species to exercise their protective effects, including the generation of bioactive substances, the competition for nutrients and adhesion sites, the lowering of vaginal pH through the production of lactate, and the modulation of host immunity.

A microbiota dysbiosis, for instance, has a direct impact on the production of microbial metabolites, and the presence of metabolites at higher or lower levels alters PTB metabolism. Short-chain fatty acids, polyamines, polyphosphates, and peptides are some of these metabolites. The other accepted pathways mentioned above may help explain why Lactobacillus spp. is protective in PTB.

It is currently unclear if altering the microbiota of the mother and the newborn by probiotic supplementation influences the risk of preterm birth and associated consequences, despite several clinical trials and meta-analyses.

The idea that maternal dysbiosis might act as a catalyst for preterm birth is supported by evidence. According to one study, probiotic therapy in late pregnancy may alter the vaginal microbiota by reversing the dysbiosis associated with more than 70% of cases of bacterial vaginosis and the rise in Atopobium. This dysbiosis can also result in preterm birth. Additional probiotics can also lower the vaginal pH to an ideal level after antibiotic therapy, encouraging the repair of the vaginal microbiota and moderating the inflammatory cascade frequently seen in preterm birth.

The use of probiotics to stop premature births has had conflicting outcomes, nevertheless.

Probiotic use during pregnancy did neither reduce or increase the risk of preterm birth before 34 weeks or before 37 weeks, according to a 2019 review.

There is still no clear evidence that using probiotics or prebiotics during pregnancy either raises or lowers the risk of preterm birth, according to another systematic review and meta-analysis conducted in 2018. The authors came to the conclusion that there is still insufficient data to justify the use of probiotics or prebiotics during pregnancy in order to avoid premature birth, bad pregnancy outcomes for the mother, or babies.