Probiotics and their immunological effect on cirrhosis of the liver

This article is part of our special edition of May 2021. Download the full edition here.

reference

MACNAUGHTAN J, Figorilli F, García-López e, et al. A double-blind, randomized, placebo-controlled study with probiotics lactobacillus caseei shirota in patients with stable cirrhosis. nutrients . 2020; 12 (6): 1651.

Study goal

to determine whether probiotic lactobacillus caseei shirota (LCS) has a positive effect on the function of neutrophils and the infection rates in patients with liver cirrhosis

draft

A double-blind, randomized and placebo-controlled study in 2 hospitals in the United Kingdom

participant

The test doctors examined 110 patients and included 92 with cirrhosis of any etiology in 2 hospitals. These patients showed relevant clinical findings that were compatible with a cirrhose diagnosis, as well as a child-Pugh score of less than 10. The patients were between 18 and 78 years old and had dispensed with alcohol consumption 2 weeks before the screening. They were assigned to the random principle (1: 1) either the intervention or placebo group, which was stratified according to alcoholic and non-alcoholic cirrhosis ectiology.

The exclusion criteria included:

• Child-Pugh score> 10
• active infection
• antibiotic treatment 7 days before the registration
• gastrointestinal bleeding
• Use of immune modulating means
• use of proton pump inhibitors
• Use of pre-, pro or synbiotics
• creatinine> 150 mmol/l
• hepatic encephalopathy II-IV
• pancreatitis
• organ failure
• liver cancer
• pregnancy

study parameters evaluated

Patients in the intervention group received a 65 ml bottle of an LCS drink with a content of 6.5 billion colonie-image units (CFU) Bacteria (Yakult Europe), which was to be taken three times a day for 6 months. The placebo group was given a similarly looking and similarly tasting drink that did not contain any bacteria. The patients received 45 bottles every 2 weeks, with the empty, used bottles being a measure of compliance. The investigators recorded clinical benchmarks, including blood and biochemical tests during screening, on days 0 and 14 as well as in months 1, 3 and 6. They collected analytes that are relevant for intestinal hypermeability in the months 0, 1 and 6.

primary result measurements

One of the primary endpoints in this study was the change in neutrophil function. The investigators assessed this using insulation and coin tubation methods in order to measure the production of reactive oxygen species (ROS) and the prevalence of phagocytosis. The additional primary endpoint included the occurrence of infections, which were evaluated by routine clinical blood chemistry.

The concentration of the cytokin profile in the plasma at different intervals until the end after 6 months. The researchers evaluated the intestinal hypermeability based on the lactulose-rhamnosis ratio in urine, venous endotoxin centers and bacterial DNA identification with polymerase chain reaction tests (PCR). The last secondary result was the assessment of the quality of life, which was carried out using the standardized SF-36 tool.

important knowledge

Overall, no significant differences in neutrophil function were observed between the intervention and placebo group. In patients with atypical neutrophil function at the beginning of the study, the 6-month LCS treatment led to a significantly higher result of ROS production compared to the placebo arm [1403 (1214–1821) Versus 1168.00 (1014–1266), p = 0.02]. This indicates an improved neutrophil function in this sub -group.

There were no significant changes in the infection episodes between the randomized groups at the end of the study. In both groups, intestinal hypermeability was also in the normal range, with the bacterial DNA positivity 10.1 % (placebo group) and 8.1 % (LCS group).

The most important result is a positive change in the cytokin profile for all participants in the LCS group of the study.

The results with plasma cytocin concentrations were not significantly different in the vast majority of the specific cytokines examined in the study. It was observed that LCS has been the middle plasma interleukin 1 beta (il1b; p = 0.04) and monocyte chemotactic protein-1 (McP-1; p = 0.04) concentration in the alcoholic subgroup. Further observations showed a reduced concentration of interleukin 17a (IL17A) in the non -alcoholic cohort ( p = 0.02). The concentrations of macrophage-inflammatory protein-1 beta (MIP-1β) were reduced throughout the LCS in the 6-month interval ( p = 0.04).

The 36-point Short Form Health Survey (SF-36) scores to evaluate the quality of life showed no significant differences between the two study arms.

practice implications

In the constantly developing landscape of understanding the role of human intestinal microbioma, a significant part of the clinical and scientific dialogue of the role that is played between the intestine and the immune system. Dearmicrobioma. This, in turn, produces a number of evidence that clarifies the mechanisms of how a changed flora contributes to alcohol -related liver diseases. In view of the fact that an imbalance in the intestinal microbioma was observed in the case of cirrhosis of the liver, the progress of the investigation in this study is logical and fascinating. This logic is now opposed to a different train of thought that postulates that intestinal dysbiosis can be associated with alcoholic liver diseases. The health of the intestinal microbioma is of crucial importance, since dysbiosis leads to intestinal inflammation and liver damage, and the subsequent restoration of the microbiota with approaches such as promoting the amount of coming bacteria could be an advantage in order to relieve the progression of the disease.

The researchers in this study strive to continue to determine whether LCS can influence the immune function in order to ultimately achieve therapeutic benefits from probiotic use in patients with cirrhosis, both alcoholic and non -alcoholic nature. This was motivated by earlier references to LCS in a smaller study that indicated a positive correlation. ^{4 While the study comes to the conclusion that a specific mechanism of action, neutrophil activation, is not noticeably influenced, it is important to note that a sub -group of the participants has been positively influenced. This activity improved to those who had a priority function of neutrophilic activity below the normal value. This is in accordance with the open-label pilot study mentioned above. 4 No side effects have been observed and there were no increase in infections for all 92 participants, which speaks for the safety of LCS in this patient group.}

The most important result is a positive change in the cytokin profile for all participants in the LCS group of the study. This indicates that a restoration of intestinal health causes the regulation of inflammatory cytokines; However, the mechanism of action seems to be independent of factors related to intestinal hypercermeability. This raises further questions for possible studies in the future.

Further questions, both in the area of ​​clinical practice and the study design, bring a number of additional questions to the fore. Are all of the same quality produced and does this affect the results? Clinical practitioners will suggest that their patient results are proof of this concept and that serious sources for therapeutic probiotics must be considered. Second, the singularity or variety of probiotic species should be considered, since more and more evidence indicates that the diversity of the intestinal microbioma correlates with improved health results. After all, the dose -dependent effect in the selection of therapeutic probiotics and its ability to deliver the desired KBE must be taken into account. Clinical observations and case studies indicate that interventions with higher KBE correlate with improved results; However, there are clear precautions and contraindications, and the "More is better" approach has its risks and limits.

clinicians have several aspiring scientific knowledge and clinical results that they have to reconcile in the implementation of probiotics and the restoration of the intestinal microbiota. The advantages clearly include improved liver health and immune function, but are not limited to it.