The Effect of Probiotics (MCP® BCMC® Strains) on Hepatic Steatosis, Small Intestinal Mucosal Immune Function, and Intestinal Barrier in Patients with Non-Alcoholic Fatty Liver Disease - PubMed (original) (raw)

Randomized Controlled Trial

. 2021 Sep 14;13(9):3192.

doi: 10.3390/nu13093192.

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Randomized Controlled Trial

The Effect of Probiotics (MCP® BCMC® Strains) on Hepatic Steatosis, Small Intestinal Mucosal Immune Function, and Intestinal Barrier in Patients with Non-Alcoholic Fatty Liver Disease

Mohamad Hizami Mohamad Nor et al. Nutrients. 2021.

Abstract

Treatment for non-alcoholic fatty liver disease (NAFLD) currently consists of lifestyle modifications such as a low-fat diet, weight loss, and exercise. The gut microbiota forms part of the gut-liver axis and serves as a potential target for NAFLD treatment. We investigated the effect of probiotics on hepatic steatosis, fibrosis, and biochemical blood tests in patients with NAFLD. At the small intestinal mucosal level, we examined the effect of probiotics on the expression of CD4+ and CD8+ T lymphocytes, as well as the tight junction protein zona occluden-1 (ZO-1). This was a randomized, double-blind, placebo-controlled trial involving ultrasound-diagnosed NAFLD patients (n = 39) who were supplemented with either a probiotics sachet (MCP® BCMC® strains) or a placebo for a total of 6 months. Multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species at a concentration of 30 billion CFU were used. There were no significant changes at the end of the study in terms of hepatic steatosis (probiotics: -21.70 ± 42.6 dB/m, p = 0.052 vs. placebo: -10.72 ± 46.6 dB/m, p = 0.29) and fibrosis levels (probiotics: -0.25 ± 1.77 kPa, p = 0.55 vs. placebo: -0.62 ± 2.37 kPa, p = 0.23) as measured by transient elastography. Likewise, no significant changes were found for both groups for the following parameters: LiverFAST analysis (steatosis, fibrosis and inflammation scores), alanine aminotransferase, total cholesterol, triglycerides, and fasting glucose. In the immunohistochemistry (IHC) analysis, no significant expression changes were seen for CD4+ T lymphocytes in either group (probiotics: -0.33 ± 1.67, p = 0.35 vs. placebo: 0.35 ± 3.25, p = 0.63). However, significant reductions in the expression of CD8+ T lymphocytes (-7.0 ± 13.73, p = 0.04) and ZO-1 (Z-score = -2.86, p = 0.04) were found in the placebo group, but no significant changes in the probiotics group. In this pilot study, the use of probiotics did not result in any significant clinical improvement in NAFLD patients. However, at the microenvironment level (i.e., the small intestinal mucosa), probiotics seemed to be able to stabilize the mucosal immune function and to protect NAFLD patients against increased intestinal permeability. Therefore, probiotics might have a complementary role in treating NAFLD. Further studies with larger sample sizes, a longer duration, and different probiotic strains are needed to evaluate the real benefit of probiotics in NAFLD.

Keywords: NAFLD; gut microbiota; intestinal permeability; mucosal immune function; probiotics.

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Conflict of interest statement

The authors hereby declare no conflict of interest.

Figures

Figure 1

Figure 1

Consolidated Standards of Reporting Trials flow diagram of the study participants. NAFLD, non-alcoholic fatty liver disease.

Figure 2

Figure 2

Immunohistochemicalstaining of CD4+ protein in the duodenal mucosa (CD4+, 400X). (a) Duodenal mucosa of a patient with NAFLD at baseline. (b) Duodenal mucosa of a patient with NAFLD after 6 months of probiotics. (c) Duodenal mucosa of a patient with NAFLD at baseline. (d) Duodenal mucosa of a patient with NAFLD after 6 months of the placebo. The arrows show brownish staining of the CD4+ T lymphocytes in the lamina propria. Semi-quantitatively, both the probiotics and placebo groups did not show any difference in the percentage of staining before and after the intervention. Staining score: 0: no staining; +: focal staining; ++: regional staining; and +++: no loss.

Figure 3

Figure 3

Immunohistochemical staining analysis of CD4+ T lymphocytes in the villi of the duodenal mucosa in NAFLD patients. There was a slight decrease in the mean count of intraepithelial CD4+ T lymphocytes observed in the probiotics group after 6 months of the intervention (from 2.30 ± 1.83 to 1.97 ± 1.50; p = 0.35), while the placebo group showed a slight increase in the mean intraepithelial CD4+ T lymphocyte count (from 2.03 ± 1.68 to 2.38 ± 4.82; p = 0.63). Both groups did not show any significant changes.

Figure 4

Figure 4

Immunohistochemical staining of CD8+ protein in the duodenal mucosa (CD8+,400X). (a) Duodenal mucosa of a patient with NAFLD at baseline. (b) Duodenal mucosa of a patient with NAFLD after 6 months of probiotics. (c) Duodenal mucosa of a patient with NAFLD at baseline. (d) Duodenal mucosa of a patient with NAFLD after 6 months of the placebo. Red arrows show brownish CD8+ T lymphocytes in the lamina propria. Semi-quantitatively, no significant post-intervention difference was seen in either the probiotics of placebo groups. Staining score: 0: no staining; +: focal staining; ++: regional staining; and +++: no loss.

Figure 5

Figure 5

Immunohistochemical staining analysis of CD8+ T lymphocytes in the villi of the duodenal mucosa in NAFLD patients. There was a significant decrease in the mean count of intraepithelial CD8+T lymphocytes observed in the placebo group after 6 months of the intervention (from 30.51 ± 16.85 to 23.51 ± 10.61, * p = 0.04), while the probiotics group showed a slight decrease in the mean intraepithelial CD8+T lymphocyte count; however, this was not statistically significant (p = 0.211).

Figure 6

Figure 6

Immunohistochemical staining of tight junction zonula occluden-1 (ZO-1) protein in the duodenal mucosa (ZO-1400X). (a) Duodenal mucosa of a patient with NAFLD at baseline. (b) Duodenal mucosa of a patient with NAFLD after 6 months of probiotics. (c) Duodenal mucosa of a patient with NAFLD at baseline. (d) Duodenal mucosa of a patient with NAFLD after 6 months of the placebo. Brownish ZO-1 IHC staining was observed in the intestinal crypts (red arrows). There was a significant reduction in ZO-1 expression in the post-intervention placebo group (Z-score = −2.86, p = 0.04) but not in the probiotics group (Z-score = −0.93, p = 0.35). Staining score: 0: complete loss; +: moderate loss; ++: focal loss; +++: very focal loss; and ++++: no loss.

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