Prophylactic probiotic ‘ineffective’ in mitigating GI permeability associated with aspirin
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Key takeaways:
- The change in gastroduodenal permeability with an aspirin challenge was not significant between probiotic and placebo arms.
- Small intestinal, colonic permeability and whole gut permeability also did not differ.
Consumption of a prophylactic probiotic supplement of Lactobacilli did not prevent or mitigate the effects of gastrointestinal permeability associated with an acute aspirin challenge in healthy individuals, data showed.
“Several chronic immune and metabolic disorders, such as inflammatory bowel disease, type 2 diabetes and nonalcoholic fatty liver disease have been associated with a disruption of the intestinal barrier resulting in increased intestinal permeability,” Taylor C. Judkins, MS, from the University of Florida, and colleagues wrote in BMC Gastroenterology.
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In addition, exercise, general life stress and use of NSAIDs also have been shown to increase intestinal permeability, they added.
“The microbial composition of the gut is therefore influential on the gut barrier suggesting that probiotics may be useful to protect against perturbations that increase intestinal permeability,” Judkins and colleagues continued. “Because NSAIDs damage the proximal small intestine, a probiotic that exhibits effects in the proximal as well as the distal intestine is of interest.”
To investigate the effect of an acute aspirin challenge on gastroduodenal barrier function, researchers conducted a 14-week randomized, double-blind crossover trial of 29 healthy individuals. Following a 2-week baseline period, participants completed a 3-week intervention, during which they received a probiotic containing two strains of Lactobacilli or placebo, followed by a 4-week washout period between interventions.
Participants completed online daily and weekly questionnaires to assess GI function, and intestinal permeability was assessed on days 7, 14 and 21 via urinary excretion of orally administered sucrose. On day 14, all participants consumed 975 mg of non-enterically coated aspirin before bed, with an additional 975 mg consumed 30 minutes before the intestinal permeability test. Stool samples were collected weekly during probiotic supplementation for microbiome analysis.
Results showed no significant change in gastroduodenal permeability between the aspirin challenge and the previous week without a challenge between probiotic (6.5 µmol) and placebo (6.3 µmol) arms. Small intestinal permeability, colonic permeability and whole gut permeability also did not significantly differ between interventions.
Researchers reported, however, that intestinal permeability significantly increased with the dose of aspirin (week 1: 3.4 µmol vs. week 2: 9.9 µmol).
Analysis of microbiota species showed F. prausnitzii “trended towards significance” with higher abundance with probiotic consumption (1.9 ± 0.4), while mean fold changes for A. muciniphila (0.88 ± 0.12), Roseburia spp. (1.55 ± 0.31) and Bifidobacterium spp. (1.03 ± 0.14) were not significantly different.
Researchers noted there were no significant differences in Gastrointestinal Symptom Rating Scale scores between the probiotic and placebo arms, although Digestion-Associated Quality of Life Questionnaire scores were lower, indicating improved quality of life, across weeks on the probiotic.
“While previous preclinical studies using a number of models show that this probiotic can maintain gut barrier functions, this dose of the probiotic combination was ineffective in preventing or mitigating the effects on GI permeability in this model using generally healthy participants and an aspirin challenge,” Judkins and colleagues wrote. “Digestion-associated quality of life was significantly better when consuming the probiotic, which deserves further investigation as does the effect of the probiotic on fecal F. prausnitzii.”
Perspective
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Gail Cresci, PhD, RD
This is an interesting, well-designed study that tested whether a probiotic supplement could protect disruption in gut barrier integrity induced by an acute aspirin challenge. While the aspirin challenge did impair the gut barrier as assessed by a nonabsorbable sugar permeability test, there were no differences in this effect between when participants consumed the probiotic vs. the placebo. Additionally, there were no differences in the select gut microbiota taxa assessed.
Researchers cited several factors that could attribute to the lack of probiotic protection, including probiotic strain-specific mechanisms, that the probiotic’s prior intestinal integrity benefits were tested in different experimental models, that the probiotic dosing may have been too low to induce a beneficial effect or that the aspirin challenge may have been too robust for a probiotic to have an impact.
Another aspect not discussed in the article could pertain to the other ingredients in both the probiotic and placebo supplements. Both supplements contained ascorbic acid, hypromellose, magnesium stearate, saccharose, potato starch, titanium dioxide and maltodextrin. While these ingredients were added as excipients, several of these components are known to beneficially support the gut barrier.
Inadequate vitamin C status is associated with small intestinal bacterial overgrowth and endotoxemia. Hypromellose is a nonfermentable dietary fiber with many beneficial health effects including supporting the gut microbiome. Potato starch is a resistant starch not digested by humans but fermented by the gut microbiota to yield short-chain fatty acids, including butyrate and lactate. Lactate can be cross-fed into butyrate by gut microbiota, and butyrate is known to support the gut barrier and gut microbiome. So, the fact that both supplements contained these beneficial ingredients could have overridden any potential benefits seen by the Lactobacillus probiotics.
Overall, this study highlights the negative effects of high-dose aspirin on the gut barrier and that further studies are warranted to assess whether prebiotics and/or probiotics could protect this from occurring.
References:
Cox L, et al. FASEB J. 2012;doi:10.1096/fj.12-219477.
DeMartino P, et al. Curr Opin Biotechnol. 2019;doi:10.1016/j.copbio.2019.10.008.
Teichmann J, et al. Front. Microbiol. 2021;doi:10.3389/fmicb.2021.640253.
Traber MG, et al. Redox Biol. 2019;doi:10.1016/j.redox.2018.101091.
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