Authors: Wenjie Cai, Kateryna Pierzynowska, Miranda Stiernborg, Jingjing Xu, Ida AK. Nilsson, Ulla Svensson, Philippe A. Melas, Catharina Lavebratt.
Published: Clinical Nutrition ESPEN 63 (2024).
The study was conducted in vivo, with animals.
Design: The mice were randomly divided into groups. All synbiotic-treated groups were compared to a control group (no DSS induction), a placebo group (DSS induction þ water) and standard IBD treatment (DSS induction þ mesalazine).
Treatment: The intervention involved administering synbiotics. The first synbiotic preparation (Synbio1) was a combination of (i) the Synbiotic 2000 ingredients (i.e. four lactic bacteria and four fibers). To determine if all constituents of Synbio1 were necessary for any anti-inflammatory effects observed, three additional synbiotics containing fewer combinations of the same pro- and prebiotics (termed Synbio2-4), were also tested in the same model.
Where and when: Lund University.
Sample size: 84 mice.
Sample criteria: Mice (both male and female) were treated with DSS to induce colitis, mimicking IBD-like symptoms. To evaluate potential sex-specific synbiotic effects.
Analysed material: Blood samples. The study’s main outcomes of interest were the synbiotics ability to modulate clinical scores, intestinal pathology, and plasma biomarkers.
Results
Compared to placebo, the Synbio1-, 2- and 3-treated groups had improved clinical scores by day 14.
Synbio1 was the only preparation that led to clinical improvements to scores comparable to those of controls. The Synbio1-and 3-treated groups also demonstrated histological improvements in the colon.
Plasma biomarker analyses revealed significant Synbio1-induced changes in plasma IL17A, VEGFD, and TNFRSF11B levels that correlated with improved clinical or histological scores.
Sex-stratified analyses revealed that most therapeutic-like effects were more pronounced in females. Sexstratified analyses showed that the clinical scores in Synbio1, 2 and 3-treated groups were significantly lower compared to the placebo group, in both male and female mice on day 14, and among females, all the Synbio1, 2 and 3 preparations alleviated clinical scores to levels comparable to those of controls by day 14.
The overall clinical scores were higher (worse clinical condition) in males compared to females in each treatment group, except for the control group, both when comparing the clinical scores on day 14 and when comparing the change (day 14 minus day 4) in clinical scores.
The Synbio1 and 3 preparations alleviated DSS-induced histological scores of the colon. To assess the effectiveness of the synbiotic preparations on the intestine, on the last day of the experiment (day 14), colon hypersensitivity was assessed by measuring the AWR, and subsequently, mice were euthanized and dissected, collecting large intestine samples (caecum and colon) for morphological and histological examination. AWR scores indicated that colon sensitivity was significantly increased in the 1% DSS-treated animals compared to the healthy control group without DSS, but neither synbiotics nor mesalazine was able to alleviate this sensitivity.
Examinations revealed that all DSS-exposed groups had significant differences from the control group, with features of inflammation detected in both colon and caecum. Compared to placebo, Synbio1 and Synbio3 treatments alleviated the histological scores of colon, but not of caecum, on day 14.
When stratifying by sex, the Synbio1- and 3-induced improvements in the colon’s histological scores remained significant in female mice only. However, there was no significant difference between male and female mice on day 14 within any treatment group.
Taken together, these results suggest that Synbio1 and 3, but not mesalazine, alleviated the DSS-induced histopathology of the colon; a finding that again could be interpreted as more pronounced among female mice (s. 78).
Compared to placebo, Synbio1 significantly increased plasma levels of IL17A, VEGFD and TNFRSF11B, which correlated with better therapeutic-like outcomes (s. 80).
Indicative results
The findings underscore the potential therapeutic benefits of specific synbiotics for IBD management. (s.74).
Collectively, these results suggest that the Synbio1, 2 and 3 preparations, but not mesalazine, were able to alleviate the clinical manifestations induced by DSS. Moreover, sex-stratified data suggest enhanced therapeutic-like efficacies among females in the DSS model. (s.77).
The preclinical findings based on the DSS colitis model suggest that Synbio1 treatment can attenuate certain symptoms and pathologies of IBD, even more effectively than mesalazine, thus supporting the continued evaluation of synbiotics in IBD management.
This finding is also important considering the generally benign side effect profile of synbiotic components, in contrast to adverse effects that some conventional IBD medications may present.
Further research is needed to validate these outcomes in human subjects (s.74).
The development of IBD is significantly associated with gut dysbiosis. Several studies in rodent models have demonstrated the potential of single-strain probiotics, mainly consisting of Lactobacillus or Bifidobacterium, for the treatment of inflammatory colitis. This motivates further efforts to test the effects of synbiotics in IBD (s.80).
Not all synbiotic preparations studied in this study appear to have the same beneficial effects. When comparing the four different synbiotic preparations in the study, Synbio1-3 were all effective in relieving colitis-related phenotypes to varying degrees, except for Synbio4, which was not observed to have any therapeutic-like effect. Since Synbio1, followed by Synbio3, were arguably the most effective, it is possible that L. paracasei (found in Synbio1 and 3 but not in Synbio2 or 4) and L. mesenterioides (found only in Synbio1) may have a greater role in relieving colitis and could work synergistically with or without the additional fiber types found in Synbio1. Future studies are warranted to explore these possibilities. (s. 81).
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