Probiotic therapy is increasingly used in the treatment of a variety of gastrointestinal diseases and chronic inflammatory conditions of the gut.1
The present study shows beneficial effects of probiotic administration in chronic stress induced intestinal epithelial barrier dysfunction. Treatment with live probiotics—Lactobacillus rhamnosus
, strain R0011 and Lactobacillus helveticus
, strain R0052 (Lacidofil)—reduced luminal bacterial adherence and translocation to the MLN of rats following chronic WAS. Animals were provided free access to probiotics in sterile drinking water and remained healthy throughout the 17 day study protocol. Provision of probiotics in sterile drinking water offers the benefits of ease of administration of such treatment compared with bolus orogastric gavage.20
This method of administration was also utilised to maintain a constant supply of live lactobacilli, which are able to transiently colonise the bowel.9
The commercially available mixture of live probiotics used in this study has been used by us previously to demonstrate effectiveness in the reduction of both bacterial attachment and colonisation, and reduction of bacterial induced mucosal inflammation in other rodent models of infectious gastrointestinal disorders.8,9
Eutamene and colleagues21
have also reported the beneficial effects of this combination of probiotics in preventing visceral hypersensitivity and increased colonic paracellular permeability, as measured by fluxes of 51
Cr‐EDTA, in rats subjected to acute restraint stress.
Stress is a common experience of daily living and the influence of stress on clinical symptoms and outcome of chronic intestinal disorders are well documented. For example, stressful life events predispose individuals to the development of functional bowel disorders, including irritable bowel syndrome.10
Moreover, stress worsens the symptoms and clinical course of Crohn's disease, and long term stress increases the number of relapses in patients with ulcerative colitis.22
In animal models of IBD, stress increases the severity of colitis and lowers the threshold for reactivation of mucosal inflammation.12
Chronic WAS in rats is extensively employed as a reproducible and robust model of chronic psychological stress, with minimal physical stress, to better mirror the experience of ongoing environmental and life stresses in humans.12
Utilising this model, investigators have shown that chronic psychological stress induces prolonged intestinal barrier dysfunction, enhanced luminal bacterial adherence and internalisation, and a mild degree of inflammatory cell infiltration into the mucosa, leading to mild mucosal inflammation.13,14
Furthermore, chronic stress contributes to sensitisation of intestinal tissue to oral antigens and the development of food allergies by increasing transepithelial permeability and luminal antigen uptake.23
Adherence to intestinal epithelial cells is a first step for colonisation and penetration of bacteria.24
Consequently, limiting access of bacteria to the apical surface of epithelial cells lining the gastrointestinal tract is important for host survival. Probiotics transiently colonise the gut and competitively exclude pathogenic bacteria from binding to the intestinal epithelium.25
The current study shows that probiotic therapy prevents adhesion of luminal bacteria to the surface of the epithelium induced by chronic psychological stress in rats. Competitive exclusion, however, is probably not the only explanation for these findings as probiotics reduced the absolute number of adherent bacteria on intestinal epithelium. In previous studies examining the effects of chronic psychological stress on gut function, we demonstrated adherence of luminal bacteria to the apical surface of enterocytes in both the ileum and colon, as well as internalisation of some microbes into the epithelium, both of which were mast cell dependent.13
In addition, there is evidence suggesting that probiotics interact with indigenous bacteria and host immune cells to modulate mucosal inflammatory processes.26
It remains to be determined however if probiotics prevent stress induced bacterial attachment and translocation via interaction with mucosal mast cells and altering host immune responses.
Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal tract through the mucosal epithelium to other sites, such as MLN.16
This process is stimulated by altered permeability of the intestinal epithelium, increased populations of luminal bacteria, and decreased host immune defences. The studies described herein show that treatment with Lactobacillus
species eliminates bacterial translocation to MLN in rats undergoing chronic stress. Our findings are in line with other investigators who have demonstrated reduced bacterial translocation to distant organs following probiotic therapy in a rat model of haemorrhagic shock.27
The precise mechanism(s) by which probiotics maintain intestinal barrier integrity, thereby eliminating bacterial translocation to MLN in rats subjected to WAS, is currently unknown. Velin and colleagues14
reported that chronic stress modulates the barrier function of the follicle associated epithelium, thereby allowing enhanced uptake of normally non‐invasive luminal bacteria. Therefore, it is possible that probiotics could elicit their beneficial effects via a reduction in antigen uptake through Peyer's patches.
With the exception of ileal baseline Isc, in the present study probiotic treatment had no demonstrable effect on enhanced epithelial conductance (representing passive permeability to ions) and elevated permeability to macromolecules in rats subjected to chronic stress. Similar to Michail and Abernathy,28
this study shows that pretreatment with probiotics inhibits an increase in short circuit current caused by epithelial cell damage, even though there was no identifiable cell damage observed in our study.
Differences in the effects caused by probiotic treatment in baseline Isc in the ileum, as opposed to the colon, could relate to differences in pathophysiological responses of the two tissues. Alternatively, lactobacilli species interactions in the colon could modulate different immune functions, compared with the ileum. In addition, the ability of probiotics to adhere to mucosal surfaces throughout the gastrointestinal tract may depend both on the quantity and quality of the probiotic employed.29
These possibilities emphasise the diversity by which probiotics may elicit their effects and, in addition, demonstrate that probiotics may have distinct functions in different disease states.29
In conclusion, we have shown that administration of Lactobacillus species to a naïve host undergoing chronic psychological stress enhances mucosal defence against luminal bacteria, by preventing bacterial adherence to the epithelial cell surface and eliminating bacterial translocation. Enhanced bacterial uptake following exposure to chronic stress may lead to an increased antigen load in the intestinal mucosa. Thus local inflammation could be initiated, which eventually leads to more diffuse intestinal inflammation. This scenario could well have implications for the observed influence of chronic stress in humans with IBD. In addition, these findings indicate that probiotics may provide a novel approach for the management of stress induced intestinal dysfunction. More in depth studies into the mechanisms of action will allow a better understanding of how probiotics target specific organs in different disease states.