Lactobacillus johnsonii YH1136 plays a protective role against endogenous pathogenic bacteria induced intestinal dysfunction by reconstructing gut microbiota in mice exposed at high altitude

Abstract

BackgroundIntestinal microbiota plays an important role in maintaining the microecological balance of the gastrointestinal tract in various animals. Disturbances in the intestinal microbiota may lead to the proliferation of potentially pathogenic bacteria that become the dominant species, leading to intestinal immune disorders, intestinal inflammation, and other intestinal diseases. Numerous studies have been confirmed that high-altitude exposure affects the normal function of the intestine and the composition of the intestinal microbiota. However, it is still necessary to reveal the changes in intestinal microbiota in high-altitude exposure environments, and clarify the relationship between the proliferation of potentially pathogenic bacteria and intestinal injury in this environment. In addition, explored probiotics that may have preventive effects against intestinal diseases.Methods and resultsC57BL/6 mice were randomly divided into three groups, a high-altitude group (HA), control group (C), and high-altitude probiotic group (HAP). The HA and HAP groups were subjected to hypoxia modeling for 14 days in a low-pressure oxygen chamber with daily gavage of 0.2 mL of normal saline (HA) and Lactobacillus johnsonii YH1136 bacterial fluid (HAP), while the control group was fed normally. L. johnsonii YH1136 was isolated from feces of a healthy Tibetan girl in Baingoin county, the Nagqu region of the Tibet Autonomous Region, at an altitude of 5000 meters. Our observations revealed that gavage of YH1136 was effective in improving the damage to the intestinal barrier caused by high-altitude exposure to hypoxic environments and helped to reduce the likelihood of pathogenic bacteria infection through the intestinal barrier. It also positively regulates the intestinal microbiota to the extent of Lactobacillus being the dominant microbiome and reducing the number of pathogenic bacteria. By analyzing the expression profile of ileal microRNAs and correlation analysis with intestinal microbiota, we found that Staphylococcus and Corynebacterium1 cooperated with miR-196a-1-3p and miR-3060-3p, respectively, to play a regulatory role in the process of high-altitude hypoxia-induced intestinal injury.ConclusionThese findings revealed the beneficial effect of L. johnsonii YH1136 in preventing potential endogenous pathogenic bacteria-induced intestinal dysfunction in high-altitude environments. The mechanism may be related to the regulation of intestinal injury from the perspective of the gut microbiota as well as miRNAs.

Korean red ginseng extract prevents bone loss in an oral model of glucocorticoid induced osteoporosis in mice

“…In addition, treatment with Lactobacillus johnsonii also prevents polymicrobial sepsis-induced liver injury and this was associated with an increase in serum IL-10 suggesting that L. johnsonii may have an overall anti-inflammatory effect. Along with the evident anti-inflammatory effect, Lactobacillus johnsonii has also been implicated in the prevention of intestinal barrier dysfunction in several models ( Chen et al, 2021 ; Wan et al, 2022 ; Bai et al, 2023 ; Lyu et al, 2023 ). This has been evidenced by improvements in tight junction proteins such as ZO-1, occludins, and claudin-1, along with reductions in circulating D-lactate, a systemic marker used to investigate intestinal barrier function.…”

“…Along with the evident anti-inflammatory effect, Lactobacillus johnsonii has also been implicated in the prevention of intestinal barrier dysfunction in several models (Chen et al, 2021;Wan et al, 2022;Bai et al, 2023;Lyu et al, 2023). This has been evidenced by improvements in tight junction proteins such as ZO-1, occludins, and claudin-1, along with reductions in circulating D-lactate, a systemic marker used to investigate intestinal barrier function.…”

Lactobacillus delbrueckii subsp. bulgaricus Alleviates Acute Injury in Hypoxic Mice

“…The function of the intestinal barrier depends on the maintenance of tight junction proteins, which are the most important structures forming the mucosal mechanical barrier and include various proteins such as ZO-1, occludin, and claudin. Dou et al [17] found that bio-selenium nanoparticles synthesized by Lactobacillus casei could upregulate ZO-1 and Occludin content reduced by hypoxia, decrease DAO content in the ileum, and protect the intestinal barrier function. Treatment with LGG combined with sucrose also increased the expression of ZO-1 and occludin in the ileum [26].…”

“…The Food and Drug Administration (FDA) and the World Health Organization (WHO) define probiotics as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host". Dou et al [16] found that Lactobacillus casei synthesizing selenium nanoparticles could effectively alleviate damage to intestinal barrier function under acute low-pressure hypoxic stress; Lactobacillus johnsonii was able to reduce potential endogenous pathogens at high altitudes, thereby preventing gastrointestinal dysfunction, with further research suggesting this preventative effect may be related to the regulation of intestinal damage [17]. Synbiotics, a combination of probiotics and prebiotics, have been proven to alleviate rat cardiac hypertrophy caused by low-pressure hypoxia [18] and improve intestinal inflammation [19].…”

Enteric glial cells aggravate the intestinal epithelial barrier damage by secreting S100β under high-altitude conditions

“…For example, HA exposure leads to a reduction in the number of acidic mucin-secreting goblet cells and mucosal layer atrophy, resulting in the disruption of the IEB [ 32 ]. HA may disrupt the IEB through altering the composition of the intestinal microbiota, breaking intestinal immune balance and reducing the levels of ZO-1, occludin, and claudin-1 expression as well [ 33 – 35 ]. Numerous studies have shown the crucial role of EGCs in maintaining intestinal homeostasis and regulating IEB function.…”