The enormous surface area of the human intestinal barrier is key to maintaining a delicate physiological homeostasis. On one hand, it must be optimized for absorption of water and nutrients; on the other hand, it must act as a tight barrier against chemical and microbial challenges – all while protecting us from unnecessary reactions to compounds that are harmful to our health. Dysfunction of the intestinal barrier is associated with many disorders through an increase in intestinal permeability, more colloquially known as leaky gut. Recent findings have highlighted the importance of the gut microbiota in maintaining proper health, and have led to the notion that specific probiotic bacterial strains may be beneficial to the intestinal barrier.
In a review published by the British Journal of Nutrition, author Dr. Peter Bron and co-authors systematically catalog the current available preclinical and clinical evidence for the use of probiotics in improving various disease states. Specifically, authors review the potential of probiotics to modulate the gut barrier in cases of bacterial and viral infection, obesity and diabetes, necrotizing enterocolitis, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).
Bacterial and viral pathogens:
Bacterial or viral pathogens pose a common challenge to the mucosal barrier of the gastrointestinal (GI) tract. To date, attenuated pathogenic bacteria have been used to study the diarrhoea-ameliorating capability of probiotics in animals, with a generally poor success rate. Rodent in vivo infection models have demonstrated that probiotics can attenuate the severity of infection caused by several gastrointestinal pathogens, including Helicobacter pylori, Citrobacter rodentium, Listeria monocytogenes and Salmonella typhimurium, among others. It should be noted that both endogenous microbiota and probiotics may act in parallel via direct and indirect mechanisms to antagonize pathogens, making it difficult to disentangle the primary contribution of the microbiota from the role of the exogenous probiotic. However, the obvious ethical challenges posed by designing well-controlled human studies means that there have been few human infection studies to date.
Obesity and diabetes:
Metabolic endotoxemia, or high levels of gut microbiota-derived lipopolysaccharide (LPS) in the plasma, is implicated in the development of metabolic diseases associated with obesity and type 2 diabetes. LPS, which is derived from the outer cell wall components of gram-negative bacteria, is typically prevented from translocating to the plasma by the intestinal barrier. In mice, Bifidobacteria have been associated with reduced intestinal LPS levels and improved mucosal barrier function. Human studies, of which there have been few, are nonetheless in agreement with mouse studies which indicate that probiotic supplementation of Bifidobacterium, or prebiotic supplementation promoting Bifidobacterium growth, may reduce the incidence of endotoxemia. Outside of Bifidobacterium, various Lactobacilli species and Akkermansia muciniphila have also been shown to positively affect metabolic disorder parameters. Authors note that these health improvements may not be entirely attributed to the bacterial species in question, as in most cases, the exact underlying mechanism driving health improvements is still unknown. Furthermore, very few studies have evaluated whether similar effects can be achieved in human studies, marking a major caveat in our scientific understanding.
Immaturity of the intestinal barrier is a defining characteristic of necrotising enterocolitis (NEC), an acute inflammatory disease with high mortality affecting low-birth weight infants. Overall, evidence from neonatal animal models suggests that probiotics can strengthen the immature gut barrier – a hallmark of NEC – thereby reducing disease severity. In the few human studies that have been conducted, probiotic administration reduced pathogen loads in the developing preterm intestine. Authors warn however, that at this time, medical experts still hesitate to recommend the routine use of specific probiotic treatment and await large and well-designed safety and efficacy trials.
Irritable bowel syndrome:
Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterised by recurrent abdominal pain and a change in stool consistency or frequency. Although the scientific debate is ongoing, studies suggest that the gut microbiota likely contributes to IBS symptoms. Reduction of IBS-like symptoms has been achieved in animal models following intentional disruption of the epithelial barrier. Studies have shown that the addition of a variety of probiotic strains, particularly the lactic acid bacteria, have the potential to restore intestinal barrier function, highlighting the promise of probiotics as a treatment option for this this syndrome. However the results of existing trials are difficult to interpret due to the use of different strains and combinations, as well as general limitations in study design. Prebiotic compounds that favor the production of lactic acid and butyrate also deserve attention, as they may be administered together with specific probiotic strains (synbiotics) to stimulate synergistic effects between probiotics, the endogenous microbiota, and their metabolites.
Inflammatory bowel disease:
Inflammatory bowel diseases, which include Crohn’s disease (CD) and ulcerative colitis (UC) are very serious inflammatory conditions of the gut that often require powerful immunosuppression to induce remission. In light of their seriousness, the authors write that it is somewhat fanciful to suggest probiotics may treat active IBD, though they may be useful in maintaining remission. Results from recent studies on CD however, have been disappointing. More promising results have been reported for the use of probiotics in inducing and maintaining remission of UC. For instance, one study found that over a period of 12 weeks, probiotic treatment was equivalent to mesalazine for the maintenance of UC remission.
In the concluding remarks, authors highlight that to date, key work on probiotics and intestinal barrier integrity has already been done in animal models and in vitro, while relatively little is known about equivalent processes in humans. Still, a variety of studies imply that mucosal barrier function can be improved by probiotic treatment, which underpins the need for studies in well diagnosed diseased populations. Only once these human studies have been completed will the scientific community have enough evidence to confidently recommend health-promoting probiotic treatments to medical practitioners and patients alike.
Bron PA, Kleerbezem M, Brummer RJ, et al. Can probiotics modulate human disease by impacting intestinal barrier function? Br J Nutr. 2017;117(1):93-107. doi: 10.1017/S0007114516004037.