Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is known for manifesting in aggressive malignancies with highly immunosuppressive microenvironments. These microenvironments exhibit weak immunogenicity, allowing the tumor to evolve and resist therapy. This randomized, single-blinded study evaluated the synergistic immunomodulatory effects of synbiotics and their impact on postoperative complications compared to probiotics alone in PDAC patients. Ninety patients randomly received either a placebo, probiotics (a mixture of ten strains of Lactobacillus, Bifidobacterium, and Streptococcus bacteria at 25 billion colony forming units (CFUs)), or synbiotics (the same as the probiotic group along with 1000 mg inulin) for 14 days before the operation and continued for one month after. The study assessed tumor tissue infiltration of CD8+T cells, interferon-gamma (IFN-γ) expression, and the concentration of inflammatory cytokines, including IL-1β, IL-6, and IL-10. The study also evaluated short-term outcomes in the patients postoperatively. The study results showed a significant increase in CD8+T cell proportion and IFN-γ expression in the synbiotics group compared to the probiotics group. Inflammatory cytokines were also significantly decreased in the synbiotic group compared to the placebo or the probiotic groups. The synbiotics group also had a remarkable reduction in bacteremia and significantly reduced rate of postoperative complications, including anastomotic leakage, diarrhea, and abdominal distension, which was an effect also seen in the probiotic group. Overall, this study demonstrates the beneficial effects of a synbiotic formulation on immune response and its contribution to reducing surgery-associated complications in PDAC patients.

Key takeaways:

• The immunomodulatory effects of synbiotics as associated with post-surgical complications in PDAC patients are unclear. This study may be the first to investigate these effects in this malignancy.
• Six-week consumption of synbiotics  and probiotics in PDAC patients significantly improved the immune response in the treatment groups compared to placebo, with a greater elevation in the expression of CD8+T cells and IFN-γ with synbiotics than probiotics. 

Access to the study: https://pubmed.ncbi.nlm.nih.gov/38662232/ 

Reference: Maher, S., Elmeligy, H. A., Aboushousha, T., Helal, N. S., Ossama, Y., Rady, M., Hassan, A. M. A., & Kamel, M. (2024). Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study. Cancer immunology, immunotherapy : CII, 73(6), 109. https://doi.org/10.1007/s00262-024-03686-6

Polyphenolic Nanoparticle-Modified Probiotics for Microenvironment Remodeling and Targeted Therapy of Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD) are chronic multifaceted disorders in the intestine that develop from complex factors, including environmental, genetic, and microbial imbalance. The development of IBD may involve impaired intestinal mucosal barrier function, microecological imbalances, and oxidative damage, making it difficult to find effective treatments. Targeting microbial imbalances is a therapeutic area of interest in IBD treatment. Probiotics like Escherichia coli Nissle 1917 (EcN) can potentially influence intestinal bacteria, but delivery challenges limit their use. Novel encapsulation strategies, such as nanotechnology, may be used to overcome the delivery challenges and address the oxidant and proinflammatory microenvironments that affect intestinal homeostasis in IBD. Polyphenols are nature-derived prebiotic active substances that modulate oxidative stress, inflammatory pathways, and the intestinal microbiota. Polyphenols have a high binding affinity to various molecules, enabling polyphenolic nanoparticle development using tannic acid (TA). This study aimed to analyze the effects of combination therapy of IBD using nanostructured polyphenol-coated EcN in modifying the IBD microenvironment and increasing gut microbiota diversity. The nanoparticles were designed by the controlled self-assembly of TA and a self-polymerizable benzene-1,4-dithiol (pBDT-TA). The antioxidant and anti-inflammatory activities of pBDT-TA nanoparticles were evaluated in vitro, exhibiting excellent scavenging activity against oxidative stress. Furthermore, the combination of the collaborative platform, EcN@SA-pBDT-TA, resulted in considerable resistance to environmental stresses and preventative efficiency in the IBD mice model. 

Key takeaways:

• The study presents a novel approach for delivering IBD therapy using polyphenolic nanoparticles.
• Polyphenolic nanoparticles may be utilized to modify probiotics and simultaneously deliver anti-IBD drugs to exert therapeutic benefits against IBDs, including colitis. 
• Combining IBD therapies represents a potential technique for remodeling the IBD microenvironment.

Access to the study: https://pubmed.ncbi.nlm.nih.gov/38720520/ 

Reference: Hu, Q., Li, J., Wang, T., Xu, X., Duan, Y., & Jin, Y. (2024). Polyphenolic Nanoparticle-Modified Probiotics for Microenvironment Remodeling and Targeted Therapy of Inflammatory Bowel Disease. ACS nano, 10.1021/acsnano.4c00830. Advance online publication. https://doi.org/10.1021/acsnano.4c00830 

Effect of prebiotic fiber on physical function and gut microbiota in adults, mostly women, with knee osteoarthritis and obesity: a randomized controlled trial

Knee osteoarthritis (OA) is a chronic and debilitating joint condition caused by progressive articular cartilage degeneration leading to joint swelling, pain, loss of function, and reduced independence. Obesity is a major risk factor for knee OA, and due to the increase in the aging population and obesity prevalence, OA has become a major contributor to rising societal costs. Prebiotics have beneficial effects on gut microbes, reducing body fat and inflammation. This study examined the effects of 6-month prebiotic intervention on physical function in adults with co-morbid obesity (BMI>30 kg/m2) and unilateral/bilateral knee OA. Fifty-four adults (92% women) randomly received 16 g/day of oligofructose-enriched inulin (prebiotic group, n=31) or maltodextrin (placebo group, n=21). The study assessed physical performance-based tests (40 m fast-paced walk test, hand-grip strength test, and timed-up-and-go test), body composition, knee pain, and quality of life. The study also evaluated serum metabolomics, inflammatory cytokines, gut microbiota, and fecal short-chain fatty acids (SCFA) as potential mechanisms of prebiotic effects. The study found significant differences in the performance-based tests from baseline at 3 and 6 months in the prebiotic group compared to the placebo. The prebiotic group also showed a trend toward significance for reduced knee pain at six months, reduced trunk fat mass (kg) at six months, and trunk fat percentage at three months compared to placebo. In the gut microbiota analysis, there were 37 amplicon sequence variants that differed, while Bifidobacterium abundance positively correlated with distance walked on the walk test and hand grip strength. Regarding serum metabolomics, the study reported an upregulation for phenylalanine and tyrosine metabolism with the prebiotic. Altogether, this study revealed the promising effects of oligofructose-enriched inulin for knee OA management in adults with obesity. Nonetheless, further trials are warranted, especially studies that include equal representation from both sexes.

Key takeaways:

• The study investigated the effects of prebiotic oligofructose-enriched inulin on physical function, gut microbiota, and other health markers in adults with knee OA and obesity. 
• Prebiotic consumption for six months demonstrated significant improvements in the physical performance-based test measurements, which positively correlated with the abundance of Bifidobacterium in the gut microbiota. 
• The study also reported a reduction in trunk fat mass and percentage and a trend toward improved knee pain. 
• As such, prebiotic fiber may be a promising intervention in knee OA management in obese adults. 

Access the study: https://pubmed.ncbi.nlm.nih.gov/38713231/ 

Reference: Fortuna, R., Wang, W., Mayengbam, S., Tuplin, E. W. N., Sampsell, K., Sharkey, K. A., Hart, D. A., & Reimer, R. A. (2024). Effect of prebiotic fiber on physical function and gut microbiota in adults, mostly women, with knee osteoarthritis and obesity: a randomized controlled trial. European journal of nutrition, 10.1007/s00394-024-03415-w. Advance online publication. https://doi.org/10.1007/s00394-024-03415-w 

A systematic review of the beneficial effects of prebiotics, probiotics, and synbiotics on ADHD

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood neurodevelopmental disorders, affecting 5-6% of children globally. ADHD manifests in various behavioral symptoms, including impulsivity, inattention, and excessive movement, which may be affected in their severity by factors such as genetic, environmental, perinatal damage, socioemotional condition during postnatal status, and food ingredients and micronutrients. As such, this systemic review employed the “gut-brain axis” theory, determining whether synbiotics and probiotics affect children with ADHD. The study analyzed randomized controlled trials (RCTs) and cohort studies that examined synbiotics and probiotics in ADHD on PubMed/MEDLINE, Scopus, EMASE, ISI Web of Science, and Cochrane Library. Nine studies were selected, including seven RCTs and two cohorts. Two RCTs investigated synbiotic supplementation in ADHD. A prospective, multicenter, double-blind, RCT in 180 participants aged 18-65 with impulsive behavior and ADHD or borderline personality for 10 weeks reported improvement in emotion regulation in patients with ADHD. Another double-blind RCT of Synbiotic 2000 (containing 4×1011 CFU of three lactic acid bacteria, Pediococcus pentosaceus 5-33:3/16:1 (Strain deposit number: LMG P20608), Lactobacillus casei ssp paracasei F19 (LMGP-17806), Lactobacillus plantarum 2362 (LMG P-20606), and 2.5 g of each of beta-glucan, inulin, pectin and resistant starch per dose) in children and adults with ADHD for 9 weeks, investigating plasma levels of immunity and inflammation markers and SCFAs. The study reported a reduction in inflammation markers in the intestine and vascular system in children with ADHD, attributed, in part, to increased SCFA levels. Therefore, the use of synbiotics in children with ADHD as adjuvant therapy may be beneficial. 

Key takeaways:

• ADHD in children and adolescents is associated in part with altered gut microbiota.
• ADHD patients may benefit from the use of probiotics and prebiotics due to their positive effects on the metabolic pathways in several psychiatric disorders. 
• This systemic review analyzed RCTs and cohort studies that examined the effects of probiotics and synbiotics that are associated with ADHD.
• Two RCTs showed that synbiotics may be effective adjuvant therapy in ADHD, but further robust studies are needed to confirm these benefits. 

Access the study: https://pubmed.ncbi.nlm.nih.gov/38623929/ 

Reference: Allahyari, P., Abbas Torki, S., Aminnezhad Kavkani, B., Mahmoudi, Z., Mousavi Hoseini, M. S., Moradi, M., Alami, F., Keshavarz Mohammadian, M., Bahoo Sele Bani, S., Abbasi Mobarakeh, K., Shafaei, H., Khoshdooz, S., Hajipour, A., Doaei, S., & Gholamalizadeh, M. (2024). A systematic review of the beneficial effects of prebiotics, probiotics, and synbiotics on ADHD. Neuropsychopharmacology reports, 44(2), 300–307. https://doi.org/10.1002/npr2.12437