Clinical

Gut Microbiome Development in Children - Atlantia

Written by Irene Cisma | Aug 22, 2023 11:00:00 PM

This blog discusses a study aimed at improving gut development in children delivered via C-section by using the probiotic Lactobacillus paracasei (LP N1115). The randomized, double-blind, placebo-controlled study involved 60 children over an 8-week period. It assessed stool consistency, bowel habits, salivary cortisol levels, fecal microbiota, and short-chain fatty acid (SCFA) metabolism. The results showed significant improvements in the probiotic group, particularly in younger children, suggesting that probiotics could play a key role in addressing the adverse effects of C-section delivery on gut health.

Table of Contents

 

Study Design and Method: 

“In this randomized, double-blind, placebo-controlled study, our aim was to investigate the efficacy and safety of Lactobacillus paracasei (LP N1115) as a probiotic to enhance digestive symptoms, salivary cortisol levels, gut microbiota composition, and short-chain fatty acids levels in infants and young children born by C-section” (Wang et al., 2021).

The study was a randomized, double-blind, placebo-controlled trial conducted over an 8-week period, involving 60 children, with 30 receiving a placebo and 30 receiving the probiotic. A total of 58 subjects completed the study. Throughout the trial, various parameters were evaluated, including stool consistency, bowel habits, salivary cortisol levels, fecal microbiota composition, and the metabolism of short-chain fatty acids (SCFAs).


Background

 

Caesarean section trends

According to new research from the World Health Organization (WHO), C-section use is rising globally, now accounting for over 21% of all childbirths. This number is set to increase, with nearly 29% of all births likely to take place by C-section by 2030. However, the potential short and long-term risks of C-section birth include postpartum sepsis, hemorrhage, respiratory distress, obesity, and allergies in children.

Importance of Gut microbiota

Gut microbiota is crucial for infant development and immune system maturation. Bacterial communities present in early life are essential for gastrointestinal maturation, immune development, and metabolism. Vaginally delivered infants have higher levels of beneficial bacteria (Bacteroides and Lactobacillus) compared to C-section delivered infants.

Probiotic potential

Lactobacillus and Bifidobacterium strains are recognized for their safety and health benefits. Probiotics may support intestinal health and resilience against infections, especially in vulnerable pediatric populations.

Participants & Procedure

 

Participants

Healthy infants and young children, both male and female, with specific inclusion/exclusion criteria, participated in the study.

Procedure

Subjects received a daily dose (2g) of probiotic or placebo samples with water or milk over 8 weeks. The parent/guardian was required to record the number of bowel movements the subjects had each day, the stool consistency, and if they experienced any abdominal pain, bloating, or flatulence. Stool and saliva samples were collected on-site at Atlantia Clinical Trials during visits 2, 3, and 4 for analysis of microbiota composition, short-chain fatty acids (SCFAs), and cortisol.

Results:

 

The study consisted of two groups: LP N1115 which received the probiotic sample, and the control group, which received the placebo. The pattern of stool data showed that the LP N1115 group moved from soft to normal and the control group remained soft. Similarly, it was determined that gender, the age of subjects represented as years and months, and LP N1115 treatment explained the largest proportion of variance in terms of the microbiota.

Upon examination of short-chain fatty (SCFAs) acids detected in the fecal samples, it was found that there was a significant difference in propanoic acid levels between LP N1115 and placebo groups, from baseline to postintervention, acetic acid and butanoic acid seemed to be significantly decreased in LP N1115 and placebo groups over time. Considering the 6–18 months subgroup, significant differences in acetic acid, propanoic acid, and butanoic acid were observed between LP N1115 and placebo groups.

“Until recently the gut microbes were viewed as harmless and of little benefit.  We now know that they play a major role in overall wellbeing. Alterations in the gut microbiota have been described in disorders as diverse as depression, diabetes, Parkinson’s disease, and autism.  We also see dramatic changes in the microbiota in those who are overweight and obese”.

  • Professor Ted Dinan, Medical Director at Atlantia Clinical Trials.

Conclusion

 

Safety and efficacy

The probiotic was safe and well-tolerated. Significant improvements in stool consistency and microbial balance were observed, particularly in younger children.

Future Directions

There is major global concern surrounding the short and long-term health implications of C-section delivery, particularly in the reduction of diversity in normal microbial composition. Clinical intervention utilizing single and multispecies probiotics have shown promising opportunities to provide therapies from an early age to treat and prevent devitalizing diseases in later life. There are mounting studies which have evaluated probiotic strains, prebiotics, and synbiotics as a way of mediating immune regulation, microbial function, and diversity in C-section delivered infants. Due to the success of such studies ((Chua et al., 2017; Garcia Rodenas et al., 2016; Hurkala et al., 2020; Korpela et al., 2018; Morais et al., 2020; Schultz et al., 2004), and the clinical benefits associated with probiotic products attributed to the objectives of this study. Namely, to evaluate the safety and efficacy of LP N1115 supplementation on gastrointestinal symptoms, salivary cortisol, gut microbiota, and SCFAs levels in a cohort of healthy, young children born by C-section.

A randomized, placebo-controlled design was employed to minimize bias when comparing efficacy data during the intervention. The probiotic was found to be safe and well-tolerated by all subjects throughout the study. Results showed that after 8 weeks of probiotic administration with a daily dose of 109 CFU, gastrointestinal symptoms, cortisol levels, and fecal characteristics were generally similar for the placebo and LP N1115 groups. However, this was expected given the ‘healthy’ nature of the study population, with any adverse effects being the primary focus. Interestingly, upon analysis of an additional subgroup (subjects ages 6-18 months), a much larger effect size between LP N1115 and placebo groups over time was found. However, Sample size was considered small in this subgroup, therefore, caution must be exercised when interpreting these findings.

Upon examination of short-chain fatty (SCFAs) acids detected in the fecal samples, it was found that there was a significant difference in propanoic acid levels between LP N1115 and placebo groups, from baseline to postintervention, acetic acid and butanoic acid seemed to be significantly decreased in LP N1115 and placebo groups over time. Considering the 6–18 months subgroup, significant differences in acetic acid, propanoic acid, and butanoic acid were observed between LP N1115 and placebo groups.

Key Takeaways

  1. Probiotic Use: Lactobacillus paracasei (LP N1115) shows potential in supporting gut health in C-section delivered children.
  2. Microbiota Differences: Probiotic supplementation can help bridge the gap in microbial diversity caused by C-section delivery.
  3. Clinical Relevance: Probiotics may offer a preventive strategy against gastrointestinal and immune-related conditions in children.

FAQs

 

What was the main goal of the study?

The main goal was to investigate the efficacy of Lactobacillus paracasei (LP N1115) in supporting gut development and overall digestive health in children delivered via C-section.

Who were the participants in the study?

The study included 60 healthy infants and young children (aged 6 months to 3 years), with both male and female participants, who were randomly assigned to receive either the probiotic or a placebo.

How long did the study last?

The study lasted for 8 weeks.

What parameters were assessed during the study?

The study assessed stool consistency, bowel habits, salivary cortisol levels, fecal microbiota composition, and short-chain fatty acid (SCFA) metabolism.

What were the significant findings regarding stool inconsistency?

The LP N1115 group showed an improvement from soft to normal stool consistency, while the placebo group remained mostly soft.

How did the probiotic affect the gut microbiota composition?

The probiotic group showed significant improvements in gut microbiota composition, particularly in children aged 6-18 months.

Were there any significant changes in short-chain fatty acids (SCFAs)?

Yes, there were significant differences in propanoic acid levels between the probiotic and placebo groups. Acetic and butanoic acids decreased in both groups over time, with notable differences in the 6-18 month subgroup.

Was the probiotic safe and well-tolerated?

Yes, the probiotic was found to be safe and well-tolerated by all subjects throughout the study.

What are the implications of this study for further research?

This study suggests that probiotic interventions could mitigate adverse effects of C-section delivery on gut microbiota. Further research is needed to explore long-term benefits and optimize probiotic formulations for pediatric use.