What’s the Latest in Prebiotic Research? – June 2023 Edition

Early life gut microbiota profiles linked to synbiotic formula effects: a randomized clinical trial in European infants 

The microbial colonization of the gastrointestinal tract starts at birth and continues during the first months of life. This is vital for gut microbiota establishment and immune system maturation. Analysis of post-birth colonization is an essential factor in understanding the strategies (e.g., infant diet) that positively modulate the process in early life. This randomized, double-blind, controlled study included 540 healthy infants to investigate the effects of a synbiotic intervention formula (IF, n=230) on the fecal microbiome, compared to a control group (CF, n=230) and a breastfed reference group (n=80). The synbiotic IF standard formula contained GOS (0.02 g/g) and the probiotic strain L. fermentum CECT5716 (at least 1.0 x 106 colony forming units/g), while the follow-on formula was enriched with 0.03 g/g GOS and 1.5 x 106 cfu/g. The control formula was similar in all components, but it did not include any prebiotics or probiotics. The infants started formula consumption within the first three days after ad libitum inclusion, maintaining it until six months old, followed by follow-on formula until 12 months old. Fecal samples were analyzed by 16S rRNA amplicon sequencing at 4, 12, and 24 months of age, in addition to measuring short-chain fatty acids (SCFAs) and other parameters like pH, humidity, and IgA. Age-dependent changes were reported in microbial profiles in terms of diversity and composition, including significant differences at four months of age in the synbiotic IF group, with higher Bifidobacterium spp. and Lactobacillaceae, and lower Blautia spp. and Ruminoccocus gnavus and relatives. A lower fecal pH and concentrations of butyrate were also reported. When comparing overall phylogenetic profiles, infants receiving the synbiotic IF were found to be closer to those fed with human milk than infants fed CF. All in all, a low overall diversity and high relative abundance of bifidobacteria and Enterobacteriaceae, with an absence of Akkermansia spp. and Faecalibactreium spp. was observed in breastfed infants and a low prevalence (<10%) in formula-fed infants at four months of age, which had higher detection at later time points in all groups. Further analysis of clinical parameters associated with the reported changes may be beneficial for developing potential disease prevention strategies. 

Key takeaways: 

  • Post-birth colonization of the infant’s gut influences health and contributes to life-long immune consequences.
  • Infant formulas enriched with synbiotics used in formula-fed infants may be beneficial by mimicking microbial changes of breastfed infants.
  • These changes may include a higher relative abundance of bifidobacteria, lower richness of the microbiota, and lower fecal pH and butyrate concentrations, with the effects mainly dependent on the ecosystem profiles of the infants.
  • Further studies analyzing the clinical parameters associated with these changes may help discover potential preventative measures for allergic diseases. 

Access to the study: https://pubmed.ncbi.nlm.nih.gov/36811568/ 

References: Lagkouvardos, I., Intze, E., Schaubeck, M., Rooney, J. P., Hecht, C., Piloquet, H., & Clavel, T. (2023). Early life gut microbiota profiles linked to synbiotic formula effects: a randomized clinical trial in European infants. The American journal of clinical nutrition, 117(2), 326–339. https://doi.org/10.1016/j.ajcnut.2022.11.012

A microbiome-targeting fibre-enriched nutritional formula is well tolerated and improves quality of life and haemoglobin A1c in type 2 diabetes: A double-blind, randomized, placebo-controlled trial

Health-related quality of life (HRQoL) is a critical health measure in subjects with type 2 diabetes (T2D) and is associated with improved self-care and metabolic outcomes. This 12-week randomized, double-blind, placebo-controlled trial investigated a prebiotic fiber-enriched nutritional formula on HRQoL and metabolic control in T2D. One hundred and ninety-two participants were randomized 2:1:1 to a prebiotic fiber-enriched nutritional formula (Active, n=95), a placebo fiber-absent nutritional formula (Placebo, n=48), or non-blinded dietary advice alone (Diet, n=49). The Active intervention contained a blend of resistant starch (RS) and oat beta-glucan (OBG) with an escalating dose over three weeks to a maximum tolerated dose of two shake packets (at least one replacing a meal), which continued for the duration of the study. The primary endpoint was a change in the core Type 2 Diabetes Distress Assessment System (cT2-DDAS) at week 12. Secondary endpoints included change from baseline to week 12 in glycated hemoglobin (HbA1c), fasting plasma glucose, body weight, systolic blood pressure, and diastolic blood pressure. At week 12, cT2-DDAS and HbA1c were significantly reduced in the Active vs Placebo. Moreover, gut microbiome sequencing revealed a significant increase in the relative abundance of Roseburia faecis and Anaerostipes hadrus, two butyrate-producing bacterial species, when comparing the Active to Placebo groups. As such, this fibre-enriched nutritional formula may be used as a complement to lifestyle and/or pharmaceutical interventions for managing T2D.

Key takeaways:

  • HRQoL is associated with improved self-care and metabolic outcomes in T2D patients. 
  • Prebiotic fiber-based supplements present potential in the management of T2D. 
  • A microbiome targeting prebiotic fiber-enriched nutritional formula improved HRQoL and metabolic health in T2D patients. 
  • The formula caused a significant increase in the relative abundance of butyrate-producing species, specifically Roseburia faecis and Anaerostipes hadrus.

Access to the study: https://pubmed.ncbi.nlm.nih.gov/36594522/ 

Reference: Frias, J. P., Lee, M. L., Carter, M. M., Ebel, E. R., Lai, R. H., Rikse, L., Washington, M. E., Sonnenburg, J. L., & Damman, C. J. (2023). A microbiome-targeting fibre-enriched nutritional formula is well tolerated and improves quality of life and haemoglobin A1c in type 2 diabetes: A double-blind, randomized, placebo-controlled trial. Diabetes, obesity & metabolism, 25(5), 1203–1212. https://doi.org/10.1111/dom.14967 

Effects of prebiotic therapy on gastrointestinal microbiome of individuals with different inflammatory conditions: A systematic review of randomized controlled trials

Inflammation is a natural response to infection or tissue damage that can have both positive and negative effects on the body. Sometimes this process can become continuous, leading to the development of chronic inflammatory diseases. It has been found that the gut microbiota is involved in the function and development of the immune system, with signs of dysbiosis shown by fecal sample analysis from patients with immune-mediated inflammatory diseases. As such, prebiotics may play a role in inflammatory diseases via their microbiome-modulating effects. This systemic review evaluated prebiotic effects on the gastrointestinal microbiome of individuals with various inflammatory conditions. Six databases were searched for applicable randomized clinical trials (RCTs) published until March 23, 2023. Thirty studies were retrieved which ranged from 12 to 135 patients and lasted one to 36 weeks with inulin-type fructans as the most commonly used prebiotic type. The majority of studies employed 16S rRNA gene sequencing for investigating the gut microbiome, and significant shifts in the gastrointestinal microbiome composition following prebiotic supplementation were reported, with the most common difference being an increase in Bifidobacterium. Only five out of the 30 trials did not show significant differences in the microbial composition of the gastrointestinal tract. These findings were attributed to factors such as loss of follow-up, small sample size, high inter-individual variability within the sample size, treatment adherence problems, and insufficient sample collection and power. Despite the heterogenicity among the studies, prebiotics remain as potential therapeutics to favorably modulate the gastrointestinal microbiome in individuals with inflammatory conditions. Nonetheless, well-designed interventional trials are necessary to elucidate the effects of prebiotics on the gastrointestinal microbiome and systemic inflammation.

Key takeaways:

  • Inflammation is necessary for healing but can harm the host if continuous and uncontrolled.
  • A link has been proposed between the inflammatory processes and the gastrointestinal microbiome composition.
  • Prebiotics may favorably modulate the gastrointestinal microbiome of individuals with various inflammatory conditions, consequently influencing the inflammatory process. 

Access the study: https://pubmed.ncbi.nlm.nih.gov/37093515/ 

Reference: Ribeiro, M. C., Levi, Y., Moraschini, V., Messora, M. R., & Furlaneto, F. A. C. (2023). Effects of Prebiotic Therapy on Gastrointestinal Microbiome of Individuals with Different Inflammatory Conditions: A Systematic Review of Randomized Controlled Trials. Probiotics and antimicrobial proteins, 10.1007/s12602-023-10075-5. Advance online publication. https://doi.org/10.1007/s12602-023-10075-5 

Effect of resistant starch consumption on appetite and satiety: A review

The global rate of obesity among adults has risen by 27.5% in the last 30 years, and the numbers of overweight and obese individuals continue to grow daily. These individuals are at an increased risk of comorbidities such as diabetes, hypertension, and various cardiac conditions. Epidemiological studies have shown an association between inadequate fiber consumption and weight gain. RS is the indigestible portion of starch that passes through the gastrointestinal tract intact, getting fermented within the colon. Since RS is not metabolized in the small intestine, the gut hormones found there that impact satiety are not signaled, contributing to an increase in satiety. RS also contains fewer calories than typical starches, further supporting weight loss. As such, this systemic review aimed to investigate the effects of RS on appetite and satiety in healthy, prediabetic, and overweight/obese adults. The study also reviewed gut hormonal changes and insulin stimulation data with post-dietary consumption. Three databases were searched for relevant RCTs published between 2009 and 2021, retrieving a total of 22 results. Sixteen of these studies were in healthy individuals and six in prediabetic or overweight/obese individuals. Out of the 16 studies in healthy individuals, nine did not observe significant improvements in appetite or satiety after RS consumption. Despite their similar designs, the studies differed in their RS type, dose, and duration, which might have influenced the inconsistency in results. Similarly, inconclusive results were reported in the studies in prediabetic adults. As the obesity epidemic continue to rise, further investigations that study RS source, amount, and duration on satiety and appetite are warranted.

Key takeaways:

  • Increasing overweight and obesity rates are significant health issues worldwide.
  • Dietary interventions with potential satiety-increasing and appetite-decreasing effects are being studied to improve these health conditions. 
  • RS has been widely studied, but results are inconsistent due to differences in RS types, dosage, and duration.
  • Further studies exploring the mechanisms of action and clinically efficacious doses of RS on satiety and appetite are advised.

Access the study: https://www.sciencedirect.com/science/article/pii/S2666154323000716 

Reference: Guo, J., Brown, P. R., Tan, L., &amp; Kong, L. (2023). Effect of resistant starch consumption on appetite and Satiety: A Review. Journal of Agriculture and Food Research, 12, 100564. https://doi.org/10.1016/j.jafr.2023.100564