Exploring the synergistic effects of vitamin D and synbiotics on cytokines profile, and treatment response in breast cancer: a pilot randomized clinical trial

Breast cancer is a significant global burden, with the highest rates of diagnosis and the leading cause of cancer-related death among female patients. Its high incidence and mortality rates emphasize the need to understand and manage the risk factors associated with this condition. These risk factors include old age, family history, mutations in the BRCA1 and BRCA2 genes, breast tissue density, and lifestyle choices such as diet and nutrition. Identifying these factors will help to find effective preventative and treatment strategies. This randomized, double-blinded, placebo-controlled pilot study investigated the effects of vitamin D and synbiotics as standalone or combination interventions for 18 weeks on the response to treatment, cytokines profile, and hormonal biomarkers in breast cancer patients undergoing neoadjuvant therapy. The study randomized 76 patients into one of four regimens: placebo, vitamin D, synbiotics, or a combination of vitamin D and synbiotics. The synbiotic supplement contained 1 x 109 colony-forming units (CFU)/g each of Lactobacillus casei, L. acidophilus, L. rhamnosus, L. salivarius, L. reuteri, Bifidobacterium lactis, B. longum, and B. bifidum with 38.5 mg fructooligosaccharides (FOS). Vitamin D was supplemented separately at a dosage of 1000 IU/day. The primary outcome was pathological complete response (pCR) versus residual tumor, where the Ki-67 marker was compared in patients with residual tumor after neoadjuvant therapy, an assessment of treatment success. The secondary outcome involved the analysis of inflammatory biomarkers to assess the impact of the interventions on the inflammatory processes. The study found no clear link between the interventions and pCR or Ki-67 index examination. Groups supplemented with vitamin D showed a significant increase in serum interleukin (IL)-6 and attenuated the reduced levels of TNF-α following neoadjuvant therapy. Vitamin D combined with synbiotics protected against decreased IL-10, which was reported only in the placebo group. The study also reported a notable nonsignificant increase in the anti-inflammatory index, specifically in the combination group receiving vitamin D and synbiotics, suggesting a synergistic anti-inflammatory effect of the combined administration. Future studies are warranted to explore the potential benefits of a synbiotic combination with vitamin D in breast cancer patients.

Key takeaways:

  • Breast cancer has the highest diagnosis and mortality rates amongst female cancer patients worldwide.
  • This study explored the potential anti-inflammatory benefits of combining vitamin D with synbiotic supplementation in breast cancer patients undergoing neoadjuvant therapy.
  • Notable nonsignificant observations in the inflammatory profiles were reported, specifically with vitamin D maintaining TNF-α levels, increasing serum IL-6, and again maintaining IL-10 levels when combined with synbiotics.
  • Further studies are needed to confirm the benefits of synbiotics and vitamin D supplementation in breast cancer patients.

Access to the study: https://pubmed.ncbi.nlm.nih.gov/39266591/

Reference: Tirgar, A., Rezaei, M., Ehsani, M., Salmani, Z., Rastegari, A., Jafari, E., Khandani, B. K., Nakhaee, N., Khaksari, M., & Moazed, V. (2024). Exploring the synergistic effects of vitamin D and synbiotics on cytokines profile, and treatment response in breast cancer: a pilot randomized clinical trial. Scientific reports, 14(1), 21372. https://doi.org/10.1038/s41598-024-72172-x

The effects of AG1® supplementation on the gut microbiome of healthy adults: a randomized, double-blind, placebo-controlled clinical trial

Given the profound impact of the gut microbiome and gut health in overall human health, there is a growing interest in new and innovative strategies to improve gut health, including the consumption of combination therapies with prebiotics, probiotics, and synbiotics. This randomized, double-blinded, placebo-controlled study examined the effect of a 4-week daily supplementation with a commercially available multi-ingredient powder (AG1®) or placebo (maltodextrin) on the gut microbiome, gastrointestinal tolerability, and other clinical safety markers in healthy subjects. AG1 is a novel synbiotic dietary supplement that includes vitamins, minerals, prebiotics, probiotics, and phytonutrients. Thirty participants (15 men and 15 women; aged 18-50, BMI of 18.5-29.9 kg/m2) provided stool samples for microbiome analysis and completed questionnaires for digestive quality of life (DQLQ), visual analog scales (VAS), and Bristol stool charts to assess stool consistency and bowel frequency before and after the 4-week intervention. AG1 supplementation enriched Lactobacillus acidophilus, Bifidobacterium bifidum, L. lactis CH_LC01, and Acetatifactor sp900066565 ASM1486575v1 while reducing Clostridium sp000435835. Concerning community function, AG1 enriched two functional pathways without diminishing any, while the placebo enriched six and diminished five. Neither treatment negatively impacted the digestive quality of life, bowel frequency, or stool consistency. Altogether, the study showed that AG1 can be consumed safely by healthy adults for four weeks with potential beneficial effects on their digestive quality of life.

Key takeaways:

  • Accumulating research has revealed that gut health directly impacts overall health; therefore, strategies to improve gut health may be very beneficial for overall health.
  • Strategies such as prebiotic, probiotic, and synbiotic supplementation may be involved in these dietary approaches as modulators of the gut microbiome.
  • This randomized, double-blinded, placebo-controlled trial supported the safe consumption of AG1® supplementation, its effects on enriching beneficial taxa in the microbiome, and improving digestive quality of life in healthy adults.

 

Access the study: https://pubmed.ncbi.nlm.nih.gov/39352252/

Reference: La Monica, M. B., Raub, B., Hartshorn, S., Gustat, A. L., Grdic, J., Kirby, T. O., Townsend, J. R., Sandrock, J., & Ziegenfuss, T. N. (2024). The effects of AG1® supplementation on the gut microbiome of healthy adults: a randomized, double-blind, placebo-controlled clinical trial. Journal of the International Society of Sports Nutrition, 21(1), 2409682. https://doi.org/10.1080/15502783.2024.2409682

Iron absorption from an iron-fortified follow-up formula with and without the addition of a synbiotic or a human-identical milk oligosaccharide: a randomized crossover stable isotope study in young Thai children

Iron deficiency anemia is a debilitating condition, particularly affecting infants and young children in low- and middle-income countries. These infants often have low iron intake, which is insufficient for their rapid growth and development at this stage. Newborns receive iron from mature human milk, containing approximately 0.3 mg/L, for up to six months. After this period, the iron provided by this source is no longer sufficient to meet their physiologic requirements. Thus, it may be necessary to introduce additional sources of iron through complementary feeding. Besides iron, human milk contains oligosaccharides known as human milk oligosaccharides (HMO). Over 200 HMO structures have been identified with the most common structure a 2’-fucosyllactose (2’FL). Recent research has demonstrated positive effects on iron absorption from supplementing infant formula with human identical oligosaccharide (HiMO) 2’FL. This randomized, controlled, single-blinded crossover study assessed the effect of adding either a synbiotic (containing galactooligosaccharides (GOS) and Limosilactobacillus reuteri DSM 17938) or HiMOs 2’FL to iron-fortified follow-up formula (FUF) on iron absorption in young Thai children. Of the 76 children (aged 8-14 months) included in the intention-to-treat analysis, 12 were anemic, 16 were iron deficient, and 5 had iron deficiency anemia. The children were allocated to a single serving of 235 mL iron-fortified (2.2 mg) FUF either alone (control group) or combined with (1) the synbiotic (400 mg/100 mL GOS and L. reuteri DSM 17938) or (2) the HiMO 2’FL (100 mg/100 mL), separated by a 3-week wash-out period. The primary comparisons were the synbiotic to the control and the 2’FL to the control. The study found that neither the synbiotic nor the 2’FL affected iron absorption. Some limitations of this study include the low dose of GOS, the inclusion of mostly non-anemic and iron-sufficient children, and the use of a formula with highly bioavailable iron to evaluate the benefits of adding synbiotics. Future studies should address these limitations and investigate whether a formula with added synbiotics may enhance iron absorption when consumed chronically.

Key takeaways:

  • The impact of adding synbiotics to infant formulas on iron absorption is uncertain.
  • This study evaluated the effect of adding a synbiotic (GOS + L. reuteri DSM 17938) and 2’FL to iron-fortified FUF on iron absorption in young Thai children aged 8-14 months.
  • The study found no significant differences in iron absorption between the different groups.
  • Further studies with new formulations and longer intervention times are warranted to investigate the chronic effects of supplementing infant formulas with synbiotics on iron absorption.

Access the study: https://pubmed.ncbi.nlm.nih.gov/39179207/

Reference: Scheuchzer, P., Sinawat, S., Donzé, A. S., Zeder, C., Sabatier, M., Garcia-Garcera, M., Ricci, C., Kamontham, T., Zimmermann, M. B., & Baumgartner, J. (2024). Iron Absorption from an Iron-Fortified Follow-Up Formula with and without the Addition of a Synbiotic or a Human-Identical Milk Oligosaccharide: A Randomized Crossover Stable Isotope Study in Young Thai Children. The Journal of nutrition, 154(10), 2988–2998. https://doi.org/10.1016/j.tjnut.2024.08.016

The effect of prebiotic fibre on the gut microbiome and surgical outcomes in patients with prosthetic joint infection (PENGUIN) - study protocol for a randomised, double-blind, placebo-controlled trial (ACTRN12623001273673)

Arthroplasty or joint replacement is a life-changing surgery for millions of people suffering from end-stage arthritis. When successful, it significantly improves pain relief, function, and independence. However, despite aseptic protocols, prosthetic joint infection (PJI) is a serious and devastating complication of arthroplasty, affecting 1-5% of patients. As the population ages, the demand for arthroplasty continues to rise, leading to more cases of PJI. This infection usually requires repeated major revision surgeries with sequentially poor results. PJI patients have a substantial risk of early death, having a five-year survival (79%), worse than that of many cancers. As such, a new treatment paradigm may be necessary. Emerging evidence suggests a link between gut microbiome health and the risk of developing PJI. Prebiotic fibers, such as resistant starch, have shown benefits in altering the microbiome and supporting metabolite production such as short-chain fatty acids (SCFAs). This eight-week randomized, double-blinded, placebo-controlled trial aims to assess the effect of a commercially available prebiotic supplement on improving the gut microbiome in patients with first-time PJI undergoing two-stage revision surgery. The study will randomize 80 patients after first-stage revision to either 34 g resistant starch or a placebo (custard powder) daily for eight weeks. This study will be the first to investigate the relationship between optimizing gut health and preventing PJI recurrence in arthroplasty patients. If the results show a positive effect of resistant starch supplementation, optimizing the gut microbiome will be recommended as a preoperative management strategy for arthroplasty patients.

Key takeaways:

  • With the increasing incidence of PJI, current prevention methods appear inadequate, requiring further precautionary strategies.
  • Preliminary data reveal that PJI patients suffer from gut dysbiosis, which may be improved with high prebiotic fiber diets.
  • Resistant starch, a prebiotic fiber, may improve gut health and treatment outcomes in PJI patients.
  • This randomized, double-blinded, placebo-controlled study will evaluate the effect of 8-week supplementation of a commercially available resistant starch on the gut microbiome in PJI patients scheduled for two-stage revision surgery.

Access the study: https://pubmed.ncbi.nlm.nih.gov/39455990/

Reference: Sharma, D. K., Ramadass, B., Callary, S. A., Meade, A., Dash, R., Clothier, R., Atkins, G. J., Solomon, L. B., & Ramasamy, B. (2024). The effect of prebiotic fibre on the gut microbiome and surgical outcomes in patients with prosthetic joint infection (PENGUIN) – study protocol for a randomised, double-blind, placebo-controlled trial (ACTRN12623001273673). Nutrition journal, 23(1), 132. https://doi.org/10.1186/s12937-024-01034-z