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27th September 2021
The gut microbiota refers to the community of bacterial species within the intestines and plays an important role in the overall health of the host. With approximately 100 trillion micro-organisms, the gut microbiota can be thought of as a virtual organ of the body that impacts on immune, metabolic and neurobehavioral traits. This wide range of effects on the host’s health are thought to be mediated by short-chain fatty acids (SCFAs), the main metabolic products of gut micro-organisms from the fermentation of dietary fibres and resistant starches.
Alterations in the gut flora are thought to be the main reason for diarrhoea, which is a common side-effect of antibiotics. One way of minimising antibiotic-induced diarrhoea is through the use of probiotics and in a 2017 systemic review, the pooled incidence diarrhoea was reduced to 8% in those using probiotics compared to 17.7% in the control group. However, what is less clear, is the impact of a probiotic on faecal levels of SCFAs and whether the use of probiotics alongside antibiotics can mitigate the changes in gut microbiota following a course of antibiotic treatment.
This was the question posed by a team from the Department of Family Medicine, Georgetown University Medical Centre, Washington, US. They set out to determine whether a yogurt containing the probiotic, Bifidobacterium animalis subsp. Lactis BB-12 (BB-12), could protect against the antibiotic-induced disruptions in both faecal SCFAs levels and gut microbiota composition. The undertook a randomised, controlled trial, in all participants received a 7-day course of amoxicillin-clavulanate 875 mg twice daily. The intervention group received a 14-day supply of a probiotic yogurt with BB-12 and the other group a control yogurt although participants were blinded to which yogurt they received. Faecal samples were collected and analysed for SCFAs and gut microbiota composition at baseline and then after 7, 14, 21 and 30 days. The primary measure of interest was changes in the level of the SCFA, acetate.
A total of 56 individuals with a mean age of 29.4 years (gender was not reported) were randomised in a 2:1 fashion to either BB-12 yogurt (38) or control. There was a significant decrease in the primary measure following administration of the antibiotics of 20.3% on day 7 in the control group. In contrast, in the BB-12 group, the corresponding reduction was lower at 15.6%. However, by day 30, acetate levels in the control group were still 25.1% lower than baseline values but only 1.6% lower in the BB-12 group. Using a measure of gut microbiota diversity, the authors found that at days 21 and 30, there was a greater decrease in diversity in the control compared to the BB-12 group.
From the participant perspective, by day 7, 42% of the control group reported at least one day of loose stools compared to 26% in the BB-12 group.
The authors concluded that concurrent administration of BB-12 with antibiotics was associated with a significantly smaller decrease in faecal SCFA levels and a more stable gut microbiota over time compared to a control yogurt.
Merenstein D et al. Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome. Nutrients 2021
31st August 2021
Atopic eczema (AE) affects between 15 and 20% of children. Although at the present time the cause remains uncertain, immune dysfunction characterised by over-production of interleukins, is clearly involved as evidenced by the effectiveness of dupilumab, which targets interleukin 4 and 13. One potential preventative therapy which has been explored in the use of probiotics, which are live micro-organisms that have been shown to reduce inflammation by suppression of various interleukins. Although there have been several reviews examining the effectiveness of probiotics in the prevention of atopic eczema, there has been heterogeneity in the findings.
This led a team from the Department of Clinical Epidemiology, University of the Philippines, Manila, Philippines, to perform a network meta-analysis to synthesize the available evidence and compare different probiotics products in the prevention of AE. The use of a network meta-analysis offer advantages over a standard meta-analysis in that the former allows for a pairwise comparison of probiotics that have not been directly compared in studies. The team included studies with patients deemed to be at high-risk of developing AE, in particular those in which a family member already had allergic disease. They considered the oral administration of any probiotic strain or mixture of strains and also included studies in which probiotics were given to mothers during pregnancy. The primary outcome of interest was the prevention of AE and the secondary outcome of interest was the presence or absence of adverse effects.
A total of 35 studies were included, 14 of which were follow-ups of completed randomised controlled trials, using 15 different probiotics mixtures and 5406 children diagnosed with AE. There were only three probiotic mixtures that appeared to reduce the risk of developing AE compared to placebo, based on the 95% confidence intervals not crossing the line of no-effect. These mixtures were Mix8, Mix3 and Mix6. Compared to placebo, Mix8 reduced the risk of developing AE by 54% (relative risk, RR = 0.46, 95% CI 0.25 – 0.85), Mix3 by 50% (RR = 0.50, 95% CI 0.27 – 0.94) and Mix6 by 42% (RR = 0.58, 95% CI 0.37 – 0.92). In subgroup analysis, 8 studies compared administration of probiotics prenatally to pregnant women and postnatally to infants. However, pairwise comparisons were not statistically significant, suggesting no real effect. There was no evidence of any adverse effects from the use of probiotics although the wide confidence intervals for the relative risks precluded any definitive conclusions.
Commenting on their findings, the authors indicated that the data did suggest a possible beneficial effect from the use of some probiotics in preventing the development of AE. They also noted that it was probiotic mixtures that seemed to be most effective and speculated that there was a likely synergistic effect between the individual probiotic species. However, they concluded that based on the available data, it was not possible to determine the optimum timing, dose or duration of probiotics for a maximal effect.
Tan-Lim CSC et al. Comparative effectiveness of probiotic strains on the prevention of pediatric atopic dermatitis: A systematic review and network meta-analysis. Pediatr Allergy Immunol 2021
6th July 2021
The British Society of Gastroenterology (BSG) has revised its 2007 guidelines on the management of irritable bowel syndrome (IBS). The latest guidance covers all aspects of the condition ranging from initial assessment and management through to secondary care referral and any subsequent investigations that should be undertaken within that setting. The guideline makes reference to the revised diagnostic Rome IV criteria produced in 2016 and notes that while the criteria are an improvement on the earlier Rome III, the revision is perhaps more restrictive and calls into question whether these latest changes can be used to diagnose irritable bowel syndrome. The BSG therefore suggests that a more pragmatic definition of the condition is provided by NICE which states that the diagnosis should be considered only if the person has abdominal pain or discomfort that is either relieved by defecation or associated with altered bowel frequency or stool form. Furthermore, the BSG guidance recommends that all patients with IBS symptoms should have a full blood count, C-reactive protein or erythrocyte sedimentation rate, coeliac serology and that clinicians should discuss the underlying diagnosis, its causes and natural history to the patients. The guidance, while accepting a limited evidence-base, advises that all patients should take regular exercise and that soluble fibre is an effective treatment for global symptoms and abdominal pain. In contrast, it recommends against the use of insoluble fibre (e.g., wheat bran) as this might exacerbate symptoms.
Medical treatments endorsed for irritable bowel syndrome include loperamide, especially where IBS is associated with diarrhoea, antispasmodics and peppermint oil and polyethylene glycol for associated constipation. Where there is uncertainty over the diagnosis or if symptoms are refractory, a referral should be made to secondary care. Several second-line therapies including tricyclic antidepressants, selective serotonin re-uptake inhibitors, linaclotide, lubiprostone and plecanatide. There is also a discussion of new and emerging treatments together with a recognition of the value of cognitive behavioural therapy, gut-directed hypnotherapy and general psychological therapies.
One area new to the guideline is the acknowledgement of a potential pathological role of an altered microbiome and which has led to interest in the use of probiotics as a potential treatment for IBS. For the guideline, the authors updated a 2018 meta-analysis on the efficacy of probiotics and found that compared to placebo, a combination of probiotics, had a significant effect on global symptoms or abdominal pain (relative risk, RR = 0.79, 95% CI 0.70–0.89). This effect was also significant for individual species including lactobacillus, Bifidobacterium and Escherichia. Based on these data, the guidance recommended that patients wishing to use probiotics should take them for up to 3 months to assess the potential benefit.
The guideline concludes that irritable bowel syndrome is a multifactorial disorder that requires a positive diagnosis and the implementation of both non- and pharmacological therapy to improve symptoms and quality of life.
Vasant DH et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. BMJ 2021