Enhanced Bacteremia in Dextran Sulfate-Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance

Thim-Uam, Arthid; Makjaroen, Jiradej; Issara-Amphorn, Jiraphorn; Saisorn, Wilasinee; Wannigama, Dhammika Leshan; Chancharoenthana, Wiwat; Leelahavanichkul, Asada

doi:10.3390/ijms23031676

Cited by 18 publications

(21 citation statements)

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“…During sepsis, the translocation of LPS, which is a major molecule of Gram-negative bacteria (the most abundant gut organism), from the intestine into the blood circulation, referred to as “leaky gut”, is a common cause of endotoxemia [ 21 , 22 , 23 ]. Meanwhile, an adaptation to the prolonged LPS stimulations in sepsis may initiate LPS tolerance [ 24 , 25 ]. Then, LPS tolerance might, at least in part, be important in sepsis-induced immune exhaustion.…”

Section: Introductionmentioning

confidence: 99%

The Regulatory Roles of Ezh2 in Response to Lipopolysaccharide (LPS) in Macrophages and Mice with Conditional Ezh2 Deletion with LysM-Cre System

Kunanopparat

Leelahavanichkul

Visitchanakun

et al. 2023

IJMS

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The responses of macrophages to lipopolysaccharide (LPS) might determine the direction of clinical manifestations of sepsis, which is the immune response against severe infection. Meanwhile, the enhancer of zeste homologue 2 (Ezh2), a histone lysine methyltransferase of epigenetic regulation, might interfere with LPS response. Transcriptomic analysis on LPS-activated wild-type macrophages demonstrated an alteration of several epigenetic enzymes. Although the Ezh2-silencing macrophages (RAW264.7), using small interfering RNA (siRNA), indicated a non-different response to the control cells after a single LPS stimulation, the Ezh2-reducing cells demonstrated a less severe LPS tolerance, after two LPS stimulations, as determined by the higher supernatant TNF-α. With a single LPS stimulation, Ezh2 null (Ezh2flox/flox; LysM-Crecre/−) macrophages demonstrated lower supernatant TNF-α than Ezh2 control (Ezh2fl/fl; LysM-Cre−/−), perhaps due to an upregulation of Socs3, which is a suppressor of cytokine signaling 3, due to the loss of the Ezh2 gene. In LPS tolerance, Ezh2 null macrophages indicated higher supernatant TNF-α and IL-6 than the control, supporting an impact of the loss of the Ezh2 inhibitory gene. In parallel, Ezh2 null mice demonstrated lower serum TNF-α and IL-6 than the control mice after an LPS injection, indicating a less severe LPS-induced hyper-inflammation in Ezh2 null mice. On the other hand, there were similar serum cytokines after LPS tolerance and the non-reduction of serum cytokines after the second dose of LPS, indicating less severe LPS tolerance in Ezh2 null mice compared with control mice. In conclusion, an absence of Ezh2 in macrophages resulted in less severe LPS-induced inflammation, as indicated by low serum cytokines, with less severe LPS tolerance, as demonstrated by higher cytokine production, partly through the upregulated Socs3.

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Section: Introductionmentioning

confidence: 99%

The Regulatory Roles of Ezh2 in Response to Lipopolysaccharide (LPS) in Macrophages and Mice with Conditional Ezh2 Deletion with LysM-Cre System

Kunanopparat

Leelahavanichkul

Visitchanakun

et al. 2023

IJMS

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“…The method of fecal microbiota analysis followed that of previous publications [ 9 , 27 , 32 , 109 , 110 ]. Briefly, feces (0.25 g per mouse) were used to extract total DNA by a power DNA isolation kit (MoBio, Carlsbad, CA, USA), and the metagenomic DNA quality was evaluated by agarose gel electrophoresis with nanodrop spectrophotometry.…”

Section: Methodsmentioning

confidence: 99%

More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-β-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages

Hiengrach

Visitchanakun

Finkelman

et al. 2022

IJMS

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(1→3)-β-D-glucans (BG) (the glucose polymers) are recognized as pathogen motifs, and different forms of BGs are reported to have various effects. Here, different BGs, including Pachyman (BG with very few (1→6)-linkages), whole-glucan particles (BG with many (1→6)-glycosidic bonds), and Oat-BG (BG with (1→4)-linkages), were tested. In comparison with dextran sulfate solution (DSS) alone in mice, DSS with each of these BGs did not alter the weight loss, stool consistency, colon injury (histology and cytokines), endotoxemia, serum BG, and fecal microbiome but Pachyman–DSS-treated mice demonstrated the highest serum cytokine elicitation (TNF-α and IL-6). Likewise, a tail vein injection of Pachyman together with intraperitoneal lipopolysaccharide (LPS) induced the highest levels of these cytokines at 3 h post-injection than LPS alone or LPS with other BGs. With bone marrow-derived macrophages, BG induced only TNF-α (most prominent with Pachyman), while LPS with BG additively increased several cytokines (TNF-α, IL-6, and IL-10); inflammatory genes (iNOS, IL-1β, Syk, and NF-κB); and cell energy alterations (extracellular flux analysis). In conclusion, Pachyman induced the highest LPS proinflammatory synergistic effect on macrophages, followed by WGP, possibly through Syk-associated interactions between the Dectin-1 and TLR-4 signal transduction pathways. Selection of the proper form of BGs for specific clinical conditions might be beneficial.

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“…Indeed, blood bacteriome was different between the patients with critical phase and febrile stage (Figure 2), despite a similar impaired intestinal permeability (positive LMER) in all participants (Table 1). In the phylum level of analysis, patients with the critical phase demonstrated predominant Bacteroidetes (highest abundance Gram-negative anaerobes in the gut), Proteobacteria (mostly pathogenic Gram-negative aerobes), and Cyanobacteria (Gramnegative bacteria with possible toxins) with lower Firmicutes (mostly Gram-positive anaerobes that dominant in healthy conditions) (Panpetch et al, 2020;Thim-Uam et al, 2022) compared with the healthy control (Figures 2A-C). Meanwhile, blood bacteriome between patients with febrile stage and control was not different (Figures 2A-C) supporting gut translocation of bacterial DNA as possible normal physiology in healthy individuals (Camilleri, 2019) that was not altered by less severe dengue infection.…”

Section: Differences Of Blood Microbiome Spectrum Between Dengue Pati...mentioning

confidence: 99%

Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease

Chancharoenthana

Kamolratanakul

Ariyanon

et al. 2022

Front. Cell. Infect. Microbiol.

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Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.

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Enhanced Bacteremia in Dextran Sulfate-Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance

Cited by 18 publications

References 93 publications

The Regulatory Roles of Ezh2 in Response to Lipopolysaccharide (LPS) in Macrophages and Mice with Conditional Ezh2 Deletion with LysM-Cre System

The Regulatory Roles of Ezh2 in Response to Lipopolysaccharide (LPS) in Macrophages and Mice with Conditional Ezh2 Deletion with LysM-Cre System

More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-β-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages

Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease

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