Research Supporting Direct Colonic Application

Research status: Medium

Though relatively few studies have been performed on colonic/rectal application of probiotics, the ones that have are promising.

Scientists have tested the efficacy of probiotics on Ulcerative Colitis using colo-rectally applied probiotics and found promising results both for:

  1. effective colonization and long-term persistence of probiotics in the mucosal lining of the intestinal wall
  2. healing of ulcered and damaged tissues and relief from symptoms of ulcerative colitis.

Additionally, the evidence supports the intuitive conclusion that the positive effects of probiotics are dose-dependent (at least for E. coli Nissle, the probiotic preparation used in the relevant trial).

As colonic/rectal application of probiotics allows for a greater concentration and absolute number of probiotics to viably reach the gut biome when compared to oral administration alone, this supports the therapeutic advantages of colonic/rectal administration, or dual-pathway administration.

 

Selected scientific literature:

1. [Human] Rectal administration of Lactobacillus casei DG modifies flora composition and Toll-like receptor expression in colonic mucosa of patients with mild ulcerative colitis.
  • Researchers found that when Lactobacillus casei DG (L. casei DG) was administered orally with 5-ASA, it failed to affect colonic flora (the stable set of bacteria adhering to the mucosal wall of the bowel) or toll-like-receptor expression. However, when oral administration of L. casei was coupled with rectal administration via enema, it successfully increased the presence of Lactobacillus species adhering to the mucosal wall (colonization) and reduced the presence of Enterobacteriaceae, a pathogenic bacteria. It also reduced inflammation by reducing TLR-4 levels.

  • “Eight weeks of oral 5-ASA did not provoke significant changes in the mucosa-associated microbiota in our UC patients (Table 3), nor did oral supplementation with L. casei DG have a significant effect on the counts of Enterobacteriaceae spp. or of Lactobacillus spp. (Table 3). L. casei DG enemas had, instead, a marked effect on the colonic microflora. While the Lactobacillus spp. cultured from biopsy specimens increased significantly, the Enterobacteriaceae spp. fell significantly (Table 3). These effects did not appear to be caused by the enemas’ mechanical action, since an 8-week period of daily rectal 5-ASA enemas had no effect on the colonic microflora of another group of UC patients studied by us (data not shown).”

    “This study provides proof of concept that the immune system activity associated to the colonic mucosa can be manipulated in UC patients via rectal administration of the probiotic strain L. casei DG. Our study, in fact, demonstrates that this particular probiotic, never tested before in UC patients, has topical, anti-inflammatory effects when 8 x 10^8 cfu is administered rectally twice daily. The possible mechanisms of action are related to alterations in the microbial flora adhering to the mucosa that can contribute to modulation of the mucosal immune response through signaling molecules, ultimately modifying the overall cytokine balance.”

    “When administered by enema, L. casei DG significantly modified the composition of the microbial flora associated to the colonic epithelium [colonization], drastically increasing the bacterial species considered less adapt to support the maintenance of an inflammatory environment.”

    Rectal administration of probiotics such as L. casei DG seems, thus, to be able to manipulate the colonic microbiota and, therefore, the mucosal immune system, producing an overall anti-inflammatory cytokine environment probably favorable to reducing mucosal inflammation and cancer risk”
2. [Human] Matthes H, et al. (2010) Clinical trial: probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN).
  • The significance of this study is that it demonstrates that the positive effects of probiotics are dose-dependent, meaning the higher the concentration/absolute number of probiotics delivered to the affected area, the superior the result. As colonic/rectal administration delivers a greater number of viable bacteria to the gut biome, its effect is expected to be superior than oral administration alone.
  • "In a double-blind study, 90 patients with moderate distal activity in UC were randomly assigned to treatment with either 40, 20, or 10 ml enemas (N = 24, 23, 23) containing 10E8 EcN [E. Coli Nissle]/ml or placebo (N = 20). The study medication was taken once daily for at least 2 weeks. After 2, 4 and/or 8 weeks the clinical DAI (Disease Activity Index) was assessed together with tolerance to treatment. Patients who reached clinical DAI <or= 2 within that time were regarded as responders. Remission rates in 57/90 PP patients were clearly dose-dependent (Figure 2): EcN 40 ml (9/17 [52.9%]), 20 ml (8/ 18 [44.4%]), 10 ml (3/11 [27.3%]), and placebo (2/11 [18.2%]). Time to remission was shorter in the 40 ml and 20 ml EcN groups than in the 10 ml EcN and placebo groups.
      3. [Mice] A new mode of probiotic therapy: Specific targeting
      • Scientists found that mice treated with a mix of Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium longum rectally recovered almost completely from colitis tissue damage, whereas oral probiotics only improved it.
      • “Rectal introduction of Y 109 (Fig. 2.3) probiotics into to [sic] the colon resulted in almost complete repair of the damaged tissue, as shown by the relatively normal colonic histology, which resembled that seen in the healthy control”
      • In the discussion, the researchers state: “Our results strongly suggest that for therapeutic purposes, the inflamed site should be directly targeted with probiotics and nutrients in order to support the epithelial cells and contribute to healing. We propose that a major effort be focused on developing a method of delivery directly to the inflamed site in the colon, while also identifying and refining the optimal combination of probiotics and nutrients capable of contributing to healing and regeneration of the inflamed site. The proposed method should be based on the targeted introduction not only of probiotic bacteria but also of nutrients such as amino acids, vitamins and other nourishing macromolecules into the colon and intestine, by administration of rectal suppositories or by their oral administration. Such precisely targeted introduction into the inflammatory site is likely to enhance adherence of the probiotic bacterial to the gut epithelium, treat the pathology, and lead to improved functioning of the colon.”