Background: Heyndrickxia coagulans is a spore-forming probiotic increasingly investigated for oral health applications due to its stability, antimicrobial activity, and ability to modulate the oral microbiota. Chewing gum has recently emerged as an innovative delivery system that may enhance probiotic dispersion and contact with oral surfaces. To comprehensively evaluate the oral health potential of H. coagulans, a four-phase research program was conducted encompassing: (1) a systematic review and meta-analysis of its clinical evidence; (2) a kinetic study assessing salivary persistence following gum administration; (3) a randomized clinical trial evaluating plaque colonization and microbiome modulation; and (4) a randomized controlled trial testing its efficacy against halitosis. Methods: Phase 1 systematically reviewed randomized and non-randomized clinical studies up to September 2025, extracting data according to PRISMA guidelines and assessing risk of bias with RoB 2.0 and ROBINS-I. Meta-analysis focused on salivary Streptococcus mutans. Phase 2 was a randomized crossover study in 10 adults who chewed probiotic gums containing H. coagulans SNZ1969® or Lacticaseibacillus rhamnosus GG (microencapsulated or not). Saliva was sampled over 2 hours to quantify CFUs and determine kinetic profiles. Phase 3 was a double-blind, placebo-controlled trial in 52 adults consuming H. coagulans gum (5×10⁸ CFU/pellet) or placebo for four weeks. Dental plaque collected at T₀–T₃ underwent qPCR for H. coagulans and 16S rRNA sequencing for microbiome analysis. Phase 4 was a parallel double-blind RCT in the same cohort assessing halitosis outcomes. Volatile sulphur compounds (VSCs)—hydrogen sulphide (H₂S) and methyl mercaptan (CH₃SH)—were measured using OralChroma™ at four time points. Results:Phase 1 included eight studies (n=30–183 participants). H. coagulans significantly reduced salivary S. mutans (pooled effect size −0.99; p<0.01) and improved gingival and periodontal parameters, although heterogeneity was high. Phase 2 showed that all probiotics peaked in saliva at T₁, with H. coagulans achieving the highest early concentrations (T₁–T₃; mean 6.1–5.6 log₁₀ CFU/mL). Probiotics remained detectable up to two hours post-chewing. Phase 3 demonstrated that H. coagulans was undetectable at baseline and in all placebo samples, but appeared in 71.4% of subjects at T₁ and 61.9% at T₂, with persistence in 9.5% at T₃. Microbiome analysis revealed transient depletion of dysbiosis-associated genera (Prevotella, Tannerella, Treponema, Neisseria, Leptotrichia) and selective enrichment of commensal taxa. Phase 4 found that both groups showed progressive VSC reductions, but declines were more pronounced with the probiotic. H₂S decreased from baseline at T₂ (p=0.008) and T₃ (p=0.031), with median levels approaching zero, although between-group differences were not significant. CH₃SH showed no significant changes. Conclusions: Across all four phases, H. coagulans demonstrated promising oral health potential. It reduced cariogenic bacteria, persisted transiently in saliva, reached and modulated the dental biofilm, and significantly lowered hydrogen sulphide levels in vivo. Effects were modest, strain- and host-dependent, and more consistent for H₂S than for CH₃SH. Chewing gum proved to be an effective delivery vehicle. Larger, longer, and mechanistically oriented trials are warranted to better define the therapeutic role of H. coagulans in preventive and adjunctive oral care.
EFFECTIVENESS OF SUGAR-FREE CHEWING GUM CONTAINING PROBIOTICS ON ORAL HEALTH
CIRIO, SILVIA
2025
Abstract
Background: Heyndrickxia coagulans is a spore-forming probiotic increasingly investigated for oral health applications due to its stability, antimicrobial activity, and ability to modulate the oral microbiota. Chewing gum has recently emerged as an innovative delivery system that may enhance probiotic dispersion and contact with oral surfaces. To comprehensively evaluate the oral health potential of H. coagulans, a four-phase research program was conducted encompassing: (1) a systematic review and meta-analysis of its clinical evidence; (2) a kinetic study assessing salivary persistence following gum administration; (3) a randomized clinical trial evaluating plaque colonization and microbiome modulation; and (4) a randomized controlled trial testing its efficacy against halitosis. Methods: Phase 1 systematically reviewed randomized and non-randomized clinical studies up to September 2025, extracting data according to PRISMA guidelines and assessing risk of bias with RoB 2.0 and ROBINS-I. Meta-analysis focused on salivary Streptococcus mutans. Phase 2 was a randomized crossover study in 10 adults who chewed probiotic gums containing H. coagulans SNZ1969® or Lacticaseibacillus rhamnosus GG (microencapsulated or not). Saliva was sampled over 2 hours to quantify CFUs and determine kinetic profiles. Phase 3 was a double-blind, placebo-controlled trial in 52 adults consuming H. coagulans gum (5×10⁸ CFU/pellet) or placebo for four weeks. Dental plaque collected at T₀–T₃ underwent qPCR for H. coagulans and 16S rRNA sequencing for microbiome analysis. Phase 4 was a parallel double-blind RCT in the same cohort assessing halitosis outcomes. Volatile sulphur compounds (VSCs)—hydrogen sulphide (H₂S) and methyl mercaptan (CH₃SH)—were measured using OralChroma™ at four time points. Results:Phase 1 included eight studies (n=30–183 participants). H. coagulans significantly reduced salivary S. mutans (pooled effect size −0.99; p<0.01) and improved gingival and periodontal parameters, although heterogeneity was high. Phase 2 showed that all probiotics peaked in saliva at T₁, with H. coagulans achieving the highest early concentrations (T₁–T₃; mean 6.1–5.6 log₁₀ CFU/mL). Probiotics remained detectable up to two hours post-chewing. Phase 3 demonstrated that H. coagulans was undetectable at baseline and in all placebo samples, but appeared in 71.4% of subjects at T₁ and 61.9% at T₂, with persistence in 9.5% at T₃. Microbiome analysis revealed transient depletion of dysbiosis-associated genera (Prevotella, Tannerella, Treponema, Neisseria, Leptotrichia) and selective enrichment of commensal taxa. Phase 4 found that both groups showed progressive VSC reductions, but declines were more pronounced with the probiotic. H₂S decreased from baseline at T₂ (p=0.008) and T₃ (p=0.031), with median levels approaching zero, although between-group differences were not significant. CH₃SH showed no significant changes. Conclusions: Across all four phases, H. coagulans demonstrated promising oral health potential. It reduced cariogenic bacteria, persisted transiently in saliva, reached and modulated the dental biofilm, and significantly lowered hydrogen sulphide levels in vivo. Effects were modest, strain- and host-dependent, and more consistent for H₂S than for CH₃SH. Chewing gum proved to be an effective delivery vehicle. Larger, longer, and mechanistically oriented trials are warranted to better define the therapeutic role of H. coagulans in preventive and adjunctive oral care.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/353918
URN:NBN:IT:UNIMI-353918