Despite it being well-established that probiotics have a role in the prevention, control, limitation and treatment of surgical diseases, there is still considerable doubt as to their success in relation to surgical procedures and this needs to change, according to a newly published editorial by Dr Katerina Kotzampassi from the Aristotle University of Thessaloniki, in Greece.
The paper, published in 'Nutrients', points out that currently literature already provides several reasons for which probiotics could be considered almost mandatory in a surgical setting, through their aptitude to: reduce systemic postoperative infections and surgical wound infections; enhance gut motility; alleviate postoperative pain; prevent antibiotic-induced diarrhea; and prevent anastomotic leaks.
Dr Kotzampassi notes that a good motivation for the increased use of probiotics might also be the reduction in hospitalisation costs.
"It is well-known that huge sums are spent to deal with surgical complications and consequently increased days of hospitalization and ICU stay, while these seem to be reduced when probiotics are used. However, to date, no large cost–benefit studies have been designed to highlight the possible role of probiotics both as an excellent “alternative” or complementary therapy, but also as an intervention which reduces hospitalization costs."
She goes on to argue that probiotics should be considered medicines, validated by the national drug registration council.
"The responsibility for their validation and the checking of their content in terms of active bacteria should pass exclusively to the national drug registration council."
Speaking about areas of research that are still lacking, she notes that it is important to look at the application of probiotics for the restoration of the other microbiomes, as now occurs for that of the skin, such as the upper respiratory tract, the oral cavity, and the anal canal, with a possible future extension to the lungs.
"Finally, more research is needed: with the deep knowledge of the detailed action of each probiotic strain, combinations of probiotics could be designed to act in different, consecutive postoperative stages, preventing negative or helping towards positive disease progress."
In a meta-analysis of 20 trials—1374 patients—probiotics/synbiotics were given for the assessment of their efficacy in reducing infection risk after abdominal surgery. Patients who received probiotics experienced a 37% reduction in the rate of SSI [RR = 0.63; 95%CI = 0.41 to 0.98] versus placebo.
In another meta-analysis of six RCTs with low heterogeneity [I2 = 11%], involving 653 colorectal surgery patients, the probiotics group demonstrated a significantly lower SSI rate than the placebo group [OR =0.62; 95%CI =0.39 to 0.99], a finding quite similar to that in general surgery patients, although colon surgery is much less ‘clean’. A problematic group of patients is those subjected to hepatectomy, being at high risk for SSI [15.2%].
A meta-analysis of four RCTs found a significant decrease [6.3%] in the subgroup receiving probiotics [RR = 0.387, 95% CI = 0.155 to 0.970, p = 0.043], without statistical heterogeneity.
Dr Kotzampassi states that there is much literature on the interactions of at least some probiotics and their metabolites on visceral pain and nociceptive process, functional dyspepsia and irritable bowel syndrome being the most representative manifestations of visceral pain.
"These bacteria are considered capable of synthesizing and releasing many neurotransmitters and neuromodulators, or stimulating entero-endocrine cells to synthesize and release neuropeptides and hormones."
She says the most well-documented research is that of Rousseaux et al., who first evaluated the ability of five well-known Lactobacilli and Bifidobacteria to induce the expression of analgesic receptors. From those five, only L. acidophilus NCFM and L. salivarius Ls-33 were found to induce a sustained increase in OPRM1 mRNA (μ-opioid) expression in human HT-29 epithelial cells, and only L. acidophilus NCFM to induce also CNR2 mRNA (cannabinoid) expression.
Then, to further validate the functional role of L. acidophilus NCFM-induced analgesic receptors, they used the colonic distension model: oral administration of NCFM for 15days (109 cfu/d) decreased normal visceral perception, allowing a 20% increase in the pain threshold, or resulted in an anti-nociceptive effect of the same magnitude as that achieved by the subcutaneously given 0.1mg/kg morphine. The authors conclude that the direct contact of L. acidophilus NCFM with epithelial cells is able to induce, via the NF-κB pathway, μ-opioid and cannabinoid receptors to mediate the normal perception of visceral pain, similar to the effects of morphine.
The doctor notes that much research has been conducted to screen the immuno-modulatory effects of probiotics: the oral administration of Lactobacillus strains was found to influence the balance of Th1⁄Th2 immune response.
She appreciates though that this effect seems to be species-, strain-, dose-, and probably time-specific.
"Therefore, we have to hope that by choosing the proper combination of probiotics, a targeted reduction in pro-inflammatory cytokines will positively engage and ameliorate postoperative pain."
Alverdy et al have shown that a low microbial diversity allows the overgrowth of mucin-degrading members of the Bacteroidaceae and Lachnospiraceae families. Pathogens such as Pseudomonas aeruginosa, Enterococcus faecalis and Serratia marcescens, with their capacity to proliferate when the microbiota become depleted, can produce collagenase and elicit intestinal inflammation, leading to anastomotic leak.
What's more, it is accepted that probiotic bacteria are responsible for short-chain fatty acid (SCFA) production, through the anaerobic fermentation of indigestible polysaccharides, such as dietary fiber and resistant starch. The SCFAs are the key energy source for colonic cells to keep intact their tight junctions and defense against opportunistic pathogens.
Thus, Dr Kotzampassi says attempts to keep the beneficial bacteria population stable or to repopulate with the health-promoting microbiota through the use of probiotics show promise.
"Why Give My Surgical Patients Probiotics"