Lipopolysaccharide [LPS, endotoxins] {60000101}

Shared Reference Notes

• [1.1] 
  - Members of the #Enterobacteriaceae family have a proinflammatory lipopolysaccharide (LPS) in the outer membrane and can exacerbate inflammation. A high relative abundance of #Enterobacteriaceae is reported in inflammatory bowel diseases, in metabolic disorders like type 2 diabetes, and in immune diseases like cancers.
• [1.2] [#Diabetes Type 1] [#Bacteroides dorei] 
  - A study performed in Finnish children found a higher abundance of Bacteriodetes dorei prior to auto-immunity and T1D development. -The Bacteriodetes phyla produce lipopolysaccharide (LPS), a potent activator of the innate immune system, that in turn increases the auto-immune response in T1D in NOD mice
• [1.3] [#Alzheimer’s disease] 
  - Lipopolysaccharide (LPS), an outer cell wall component of Gram-negative bacteria that can be highly pro-inflammatory, can enhance Aβ accumulation in brain and induce cognitive dysfunction. - AD patients show higher LPS levels in blood plasma, and neocortex and hippocampus. - LPS can also cause chronic neuroinflammation, nerve cell death in entorhinal cortex, and impairment of synaptic plasticity of neurons in hippocampus.
• [1.4] 
  - Infants born in Finland and Estonia, where early-onset autoimmunity is common, were exposed to lipopolysaccharide (LPS) primarily from Bacteroides highly abundant in their microbiomes. - Infants born in Russian Karelia, where autoimmunity is less prevalent, were exposed to a structurally distinct LPS from Escherichia coli. - Bacteroides LPS inhibits innate immune activation by E. coli LPS, providing evidence that early life colonization by immune-silencing microbiota may hinder immune education and enhance susceptibility to autoimmune disease.
• [1.5] [#Liver fibrosis] 
  - Intestinal HDL is not routed to the systemic circulation. Rather, in the form of HDL3, it is directly transported to the liver through the hepatic portal vein. - There, it sequesters bacterial lipopolysaccharide from the gut that can trigger inflammation and liver damage. - In various models of liver injury, loss of enteric HDL exacerbated pathology. - By contrast, drugs elevating intestinal HDL improved disease outcomes.
• [1.6] [#Parkinson’s Disease] 
• [1.7] [#Rheumatoid Arthritis] 
  - RA patients display increased levels of serum markers of gut permeability and damage and cellular gut-homing markers, both parameters (LPB, LPS, and I-FABP) positively correlating with disease severity. - Arthritic mice display increased gut permeability from early stages of disease, as well as bacterial translocation, inflammatory gut damage, increases in interferon γ (IFNγ)+ and decreases in IL-10+ intestinal-infiltrating leukocyte frequency, and reduced intestinal epithelial IL-10R expression. - Both arthritogenic bacteria and leukocytes are required to disrupt gut-barrier integrity. - Exposing intestinal organoids to IFNγ reduces IL-10R expression by epithelial cells and that mice lacking epithelial IL-10R display increased intestinal permeability and exacerbated arthritis. - Treatment of mice with AT-1001, a molecule that prevents development of gut permeability, ameliorates arthritis.
• [1.8] [#Colon polyps] [#Bacteroides fragilis] 
  - BF is enriched in patients with polyps > inflammatory cytokines in the mucosa adjacent to polyps. - BF from polyps is enriched for LPS biosynthesis genes, activates TLR4, and induces IL-12 > induce a pro-inflammatory response. - Presence of LPS genes and elevated expression of LPS are found in polyp tissues.
• [1.9] 
  - LPS > triggers an immune response along with inflammation and immune-cell infiltration. - LPS > In the liver > causes inflammation by stimulating immune cells.
• [#Alzheimer’s disease] - LPS > Damage the blood-brain barrier so that it can enter the brain > hinder the outflow of Aβ from cells > neuroinflammation and the accumulation of neuronal Aβ in AD > induce hyperphosphorylation of tau protein.
• - LPS > activating the TLR4 signal > promoting tumor cell metastasis and tumor angiogenesis > deterioration of #Cancer
• - LPS > downregulate the expression of Fra-1 > reducing the inhibitory effect of Fra-1 on the proliferation of #Cervical cancer cells > development of #Cervical cancer.
• [1.11] 
  - Severe Covid > higher abundance of four microbial species (i.e., #Burkholderia contaminans, #Bacteroides nordii, #Bifidobacterium longum, and #Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes > further associated with host immune response. - The abundance of Bu. contaminans > associated with higher levels of inflammation biomarkers and lower levels of immune cells. - human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in #Covid-19 patients. - The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness > associated with circulating inflammation biomarkers and immune cells. - proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.
• [1.12] 
  - The bacterial lipopolysaccharides (LPSs) > promote the profibrotic activation of intestinal fibroblasts > increased nuclear factor-κB (NF-κB)-light-chain-enhancer of activated B cell promoter activity > collagen contraction
• [1.13] [#Sleep Deprivation] 
  - #Streptococcus was negatively correlated with the concentration of fecal #Butyrate and positively correlated with the KEGG pathway of lipopolysaccharide biosynthesis.
• [1.14] [#Parkinson’s Disease] 
  - High levels of LPS have been shown to activate vagal afferent neurons, resulting in hypophagia (reduction in food intake and eating behavior) and weight loss – common non-motor symptoms of PD
• [1.15] [#Prostate cancer] [#High Fat Diet, #Western-style diet] 
  - HFD promoted inflammatory PCa growth. - The expression of Hdc, the gene responsible for #Histamine biosynthesis, and #Histamine levels were upregulated in large prostate tumors of HFD-fed mice, and the number of mast cells increased around the tumor foci. - HFD intake induced gut dysbiosis, resulting in the elevation of serum lipopolysaccharide (LPS) levels. Intraperitoneal injection of LPS increased Hdc expression in PCa.
• [1.16] 
  - LPS hampers the intestinal barrier function and activates different immune cells, which in turn produce proinflammatory cytokines that cross the BBB and act on neurons and glial cells, leading to neuroinflammation and neuronal cell death
• [1.17] [#Multiple Sclerosis, #Periodontal disease] [#Porphyromonas gingivalis] 
  - in periodontitis-diseased tissues, P. gingivalis was present, but not much LPS was evident in tissues. - these bacterial lipids accumulate in structures in blood vessels that can lead to thickening or blockages called atheromas. - in the blood of MS patients, and they found that the bacterial lipid levels were lower in MS patients, a very surprising result. They expected, if anything, that patients with the autoimmune disease would have more lipid present.
• [1.18] [#Metabolic Dysfunction-associated Steatohepatitis, #Metabolic associated fatty liver disease] [#TMA] 
  - A shift in the metabolic function of intestinal bacteria is predominantly caused by dysbiosis. In the intestine, it leads to an increase in the permeability of intestinal mucosa for LPS and ultimately causes chronic inflammation. Concentration of bacterial metabolites in the blood, such as trimethylamine which is metabolized in the liver to trimethylamine-N-oxide (#TMAO) correlates with the severity of #Steatohepatitis
• [1.19] [#Diabetes Type 2] 
  - LPS acts as a strong stimulant for the release of cytokines, which are key inducers of insulin resistance. - The bacterial lipopolysaccharide (LPS) from #Escherichia coli has been shown to exhibit major effects on insulin sensitivity
• [#Diabetes Type 1] - lipopolysaccharides biosynthesis in #Bacteroides MAGs (metagenome-assembled genomes) and #Sulfate reduction in #Anaerostipes MAGs as functional signatures of MAGs with positive IA-association (Islets autoantibody)
• [#Diabetes Type 1] - LPS produced by the #Bacteroides species in gut microbiota has immunoinhibitory properties that may impede early immune education and contribute to the development of T1D.
• [1.21] [#Behcet’s Disease] [#Butyrate, #Lactate] 
  - These results showed that the gut microbiota in BD patients was enriched with lactic acid-producing bacteria, #Sulfate-reducing bacteria, and some opportunistic pathogens but lacked #Butyric acid-producing bacteria and methanogenic bacteria. - In mice receiving BD feces, it was observed that the intestinal barrier was disrupted with low expression of tight-junction proteins, leading to LPS release into circulation. - enrichment of #Bilophila, Alistipes, and #Paraprevotella was observed in the BD-recipient group.
• [1.22] [#Parkinson’s Disease] 
  - In patients with PD > decrease in the abundance of hydrogen-producing bacteria and lower serum decrease in the abundance of hydrogen-producing bacteria and lower serum lipopolysaccharide-binding protein levels, which suggests greater intestinal permeability to this lipopolysaccharide-binding protein levels in patients with PD, which suggests greater intestinal permeability to this lipopolysaccharide
• [1.23] [#Alzheimer’s disease] [#Fusobacterium nucleatum] [#Amyloid-beta] 
  - antibodies to F. nucleatum can be detected in the serum of patients with AD or cognitive impairment. - F. nucleatum activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. - LPS promoted the proliferation of brain microglia - F. nucleatum-induced periodontitis resulted in the exacerbation of Alzheimer’s symptoms in 5XFAD mice including increased cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the mouse cerebrum. - The stimnuli like LPS, Aβ or IFN-γ would activate microglial M1 phenotype, leading to the expression of pro-inflammatory cytokines and irreversible neuron loss. - The main known virulence factors of F. nucleatum include FadA, Fap2, and LPS
• [1.24] [#Alzheimer’s disease] 
  - #Bacteroides fragilis in the human gastrointestinal (GI) tract generates > neurotoxin #BF-LPS > #BF-LPS leaks out of the GI tract, crosses the blood brain barrier via the circulatory system, and accesses brain compartments > inreases inflammation in brain cells and inhibits neuron-specific neurofilament light (NF-L,) a protein that supports cell integrity > deficiency of NF-L > consequent atrophy of the neuronal cytoskeleton and the disruption of synaptic organization.
• [#Alzheimer’s disease] - LPS and other pro-inflammatory stressors strongly induce a defined set of NF-kB (p50/p65)-sensitive human microRNAs, including a brain-enriched Homo sapien microRNA-30b-5p (hsa-miRNA-30b-5p; miRNA-30b) > upregulated in AD brain and LPS-stressed human neuronal-glial (HNG) cells in primary culture targets the neurofilament light (NF-L) chain mRNA 3’-untranslated region (3’-UTR) > post-transcriptional downregulation of NF-L expression observed within both AD and LPS-treated HNG cells > A deficiency of NF-L is associated with consequent atrophy of the neuronal cytoskeleton and the disruption of synaptic organization. - Increased miRNA-30b expression induces neuronal injury, neuron loss, neuronal inflammation, impairment of synaptic transmission, and synaptic failure in neurodegenerative disease and transgenic murine models.
• [1.25] [#Parkinson’s Disease] 
  - high serum LPS levels in PD patients can reflect altered intestinal permeability already in the early stages of the disease. - animal models of PD > administration of LPS (stereotaxic, systemic, or intranasal) can reproduce the specific motor features of PD. - LPS-elicited neurotoxicity in PD. - Altered levels of LPS can, in turn, activate Toll-like receptors (TLRs), a family of receptors that constitute a sort of immune system against bacteria. Overstimulation of this system may provoke proinflammatory reactions, as well as enteric neuroglial activation, eventually eliciting α-Syn pathology
• [1.26] [#Isoflavone] [#Isoflavone diet, #Phytoestrogen-free (phyto-free) diet] 
  - LPS extracted from feces of mice fed an ISO diet induced increased production of anti-inflammatory cytokines from bone marrow-derived macrophages relative to fecal-LPS isolated from mice fed a PF diet.
• [1.27] [#Antibiotic Therapy, #Condition of chronic stress] 
  - stressor exposed mice had significantly altered community structure of their gut microbiota, with decreased abundance of the genus #Bacteroides and increased abundance of the genus #Clostridium. This was accompanied by increased circulating levels of IL-6 and monocyte chemoattractant protein 1 (MCP-1). - In a follow-up experiment, animals were fed an antibiotic cocktail in the morning and evening by oral gavage, beginning three days before the stressor and continuing to the end of the experiment. Antibiotic treatment prevented the increases in IL-6 and MCP-1. - mice receiving the stressor had elevated hepatic portal blood levels of LPS (from the gastrointestinal draining vein) and elevated mRNA expression of IL-1β, IL-6, and TNF in the hypothalamus, though no changes in circulating cytokines. Pretreatment with L. farciminis, antibiotics, and ML-7 all prevented these increases.
• [#Depression] - Depressed individuals had ↑ circulating IgM and ↑ IgA antibodies against LPS, indicating increased bacterial translocation. - Individuals with depressive and/or anxiety disorders had altered plasma levels of: ↑ LPS, ↑ #Zonulin, and ↑ fatty acid-binding protein 2, as well as an overrepresentation of LPS biosynthesis genes in the fecal microbiome. - Couples with hostile marital interactions had altered circulating: ↑ LPS binding protein (LBP), and ↑ CRP, and individuals with a history of mood disorders had altered circulating levels: ↑ ratio LBP/sCD14 and ↑ CRP
• [1.28] [#Alzheimer’s disease] [#Saccharomyces boulardii] [#Amyloid-beta] [#Probiotic] 
  - S. boulardii significantly reduced the elevated levels of serum interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as hippocampal levels of NLRP3 and caspase-1 in the LPS model. - S. boulardii alleviated amyloid-β deposition in the rat hippocampus. - S. boulardii could inhibit memory impairment, neuroinflammation, and amyloid-β accumulation induced by LPS, possibly by modifying the gut microbiota.
• [1.29] 
  -lipopolysaccharide biosynthesis was overrepresented in Case and PreCase subjects suggesting that #Sarcopenia is associated with a pro-inflammatory metagenome.
• [#Parkinson’s Disease] - of the 29 species that are reduced in PD, only 1 is a canonical Gram-negative organism, #Prevotella copri, which interestingly, produces an LPS that not only does not induce inflammation, but can inhibit TLR4 activation by others. - Eleven of the 55 species that are enriched in PD are canonical Gram-negative organisms including those with highly stimulatory LPS (#Escherichia coli, #Klebsiella species, and #Porphyromonas asaccharolytica).
• [1.31] 
  - #Tomato > Fruitflow when administered over 4 wk at 2×150 mg Fruitflow per d > significantly reduced fasting plasma and urine #TMAO as well as plasma LPS from baseline to the end of intervention.
• [1.32] 
  - Vagus nerve stimulation decreases the neuroinflammatory response to systemic administration of lipopolysaccharides and induces an anti-inflammatory microglial phenotype in an AD model. - Stimulation of the vagus nerve > release #Acetylcholine, which has an anti-inflammatory effect on macrophage gene expression in the periphery.
• [#Alzheimer’s disease] - methylamine trimethylamine N-oxide (#TMAO), enhance BBB integrity by altering expression of annexin A1, a tight junction protein. - #TMAO limit LPS-mediated memory impairment by limiting microglial and astrocyte-mediated neuroinflammation. - BBB breakdown is well documented in AD.
• [1.33] [#Sphingomyelin] 
  - Increased levels of lipopolysaccharides (LPS) associated with an altered gut microbiome may trigger the activation of sphingomyelinases (SMAse) and the hydrolysis of SM to produce #Ceramides.
• [1.34] [#Parkinson’s Disease] 
  - LPS can activate microglia and promote neurodegeneration
• [1.35] [#Atherosclerosis, #CVD] [#TMA, #TMAO] 
• [1.36] 
  - Toll-like receptors (TLR) enable host innate immune system to identify pathogen-associated molecular patterns (PAMP) of microbes, such as lipopolysaccharide (LPS), lipoproteins or #Flagellin
• [1.37] [#Short Chain Fatty Acid] [#High Fat Diet] 
  - HF diets affect the composition of the gut microbiota limiting SCFAs production. - It reduces the diversity of bacterial strains and the abundance of #Bacteroidetes, promoting the growth of #Firmicutes and #Proteobacteria. - Animal studies confirmed the rise in pro-inflammatory cytokines and plasma lipopolysaccharide (LPS), with consequent pro-inflammatory signalling induced by NF-kB.
• [1.38] 
  - #Anthocyanins inhibit LPS-induced microglial activation in BV2 microglial cells by inhibiting NF-κB translocation into the nucleus and consequently cytokine release including #Nitric Oxide and prostaglandin E2 release
• - that repeated treatment of sodium #Butyrate attenuated LPS-induced depressive behaviors while simultaneously attenuating microglial activation in the hippocampus, possibly through epigenetic regulation of various promoter elements
• [#Catechins] - A major #Green Tea catechin, #Epigallocatechin gallate (EGCG) has many neuroprotective abilities, neuroinflammation being just one of them. Pretreatment of outbred ICR mice with EGCG for 3 weeks (1.5 and 3 mg/kg/day) prior to LPS injection for 7 days prevented the LPS-induced memory impairment and apoptotic neuronal cell death.
• [#Depression, #Major depressive disorder] - elevated GIT permeability with an increased translocation of LPS from gram-negative bacteria plays a significant role in the pathophysiology of MDD
• - #Caffeic acid, at a dose of 30 mg/kg body weight in mice, prophylactically inhibited LPS-induced sickness behavior specifically by reducing cytokine production in serum and brain thus eliciting a protective effect against neuropathologies associated with #Depression
• [#Depression] - a single injection of LPS is associated with elevated systemic and central inflammatory mediators and significant cognitive deficits
• [#Epigallocatechin gallate] - Similar to EGCG, #Resveratrol was shown in neuron-glial primary cultures to inhibit LPS-induced microglial activation and subsequent production of TNFα, #Nitric Oxide and IL-1β likely through modulation of inflammasome signaling
• - Ligusticum officinale is an anti-inflammatory plant used in oriental medicine which is rich in #Ferulic acid and potently can attenuate NF-κB activation in BV2 microglial cells following LPS stimulation.
• [1.39] [#Porphyromonas gingivalis] 
  - Cells of Paneth autonomously sense LPS via MyD88-dependent TLR, then stimulate antimicrobial cytokines and trigger the downstream NF-κB pathway, which subsequently regulates the production of Th17 cells or Tregs (LPS from P. gingivalis induces a stronger Th2 response while #Klebsiella pneumoniae induces a stronger Th1 response)
• [#Alpha-synuclein] - lipopolysaccharides which are known to be present in the outer membrane of Gram-negative bacteria, including #Desulfovibrio bacteria, may be an additional virulence factor. Lipopolysaccharides have been shown to modulate alpha-syn aggregation
• [1.41] 
  - endotoxin may prevent adipocyte browning and impair mitochondrial respiration, biogenesis and dynamics in human adipocytes, thus contributing to #Obesity-related metabolic dysfunction, including dyslipidaemia and ectopic AT deposition in T2DM.
• [1.42] 
  - #Butyrate nourishes the colonocytes and helps preserve gut barrier function (tight junction proteins expression and mucus production), meanwhile reducing LPS circulation.
• - Circulating LPS inhibit adiponectin receptors, which is anti-inflammatory.
• - LPS activate the endocannabinoid system (cCS), increasing food intake.
• - Circulating LPS activate Toll-like receptors, which are pathogen scavengers, and increase inducible #Nitric Oxide synthase (iNOS), a biomarker of stress; both TLR and iNOS increase inflammation and energy expenditure.
• [#Obesity] - inflammation driven by lipopolysaccharides (LPS) and other microbial molecules, however, has been associated with greater adiposity and insulin resistance
• [1.43] [#Short Chain Fatty Acid] 
  - #Hypertension groups > low gut microbial diversity and some distinctive taxa, depleted SCFA-producing bacteria, such as Ruminococcacea and #Faecalibacterium, and enriched LPS-producing gram-negative bacteria, such as #Bacteroidales, #Negativiticus, and #Megamonas,
• [1.44] [#Alpha-synuclein] 
  - #Desulfovibrio is a #Hydrogen sulfide (H2S) and lipopolysaccharide (LPS)-producing bacteria. - LPS-treated mice would present intestinal hyperpermeability and a higher level of pathological α-syn accumulation
• [1.45] [#TNF-alfa] 
  - In healthy individuals, #Bilophila was negatively correlated with LPS-induced production of TNF-α
• [#Depression] [#TNF-alfa] - lipopolysaccharide (LPS) produced by #Veillonella could stimulate the release of TNF-α, IL-1, #IL-6 and #IL-10 within Toll-like receptor (TLR) pathways
• [1.46] 
  - Toll-like receptor-4 (TLR-4) is expressed in human sperm and Sertoli cells, and endotoxin acts as a ligand for TLR-4. - activated inflammatory factors, which can cause vascular endothelial damage, disruption of the blood-testis barrier, and impair spermatogenesis and viability,ultimately contributing to #Male Infertility;
• [1.47] [#Postmenopausal osteoporosis] 
  - #Estrogen deficiency, the permeability of the gut increases leading to the translocation of harmful pathogens and the production of antigens (LPS) in the systemic circulation.
• [1.48] 
  - #Bacteroidetes produce lipopolysaccharides (LPS), which are interestingly offensive to the gut mucosal barrier and play a role in retina inflammation by increasing interleukin-6 (#IL-6)
• [1.49] [#Colorectal cancer] [#Carnobacterium maltaromaticum] 
  - C. maltaromaticum could restore the gut barrier function at the early time points. - The restoration of gut barrier function was associated with increased expression of a number of associated markers, including ZO-1, #Occludin, and E-cadherin in mouse CRC models, enhanced thickness of colonic mucus layer, along with decreased paracellular gap and serum LPS level. - VDR signaling was activated significantly in C. maltaromaticum-treated mice, and the tumor-suppressive effect of C. maltaromaticum was dependent on VDR.
• - TLR4 is a pattern-recognizing receptor that recognizes exogenous ligands, such as bacterial LPS. - activation of TLR4 by LPS induces the activation of NF-κB and mitogen-activated protein kinase (MAPK) pathways and ultimately elicits the release of proinflammatory cytokines. - The activation of TLR4 is a key etiological condition for the development of #Atherosclerosis.
• [1.51] 
  - #Butyrate can reduce #Oxidative stress and pro-inflammatory activity by maintaining the integrity of the gut barrier and limiting the translocation of bacteria and bacterial components such as lipopolysaccharide into the systemic circulation
• [1.52] [#Prostate cancer] 
  - PCA growth was facilitated by the nuclear factor-beta (NF-B)-IL6-STAT3 axis being triggered by an intratumoral increase of LPS
• [1.53] 
  - Preclinical studies have verified that subdiaphragmatic #Vagotomy blocked the development of #Depression-like behaviors in rodents after LPS injection or #Fecal Microbiota Transplantation (FMT) from Chrna7 knock-out mice with #Depression-like behaviors
• [1.54] 
  - Increased gut permeability results in increased entry of LPS, a cell wall component of gram-negative gut flora, to reach the Liver, which activates TLR4, thus promoting liver carcinogenesis and #Liver fibrosis by triggering chronic inflammation.
• [1.55] 
  - inflammation model mimicking bacterial infection using lipopolysaccharide, the expression of many Tas2rs was significantly upregulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. - inflammation > Tas2r gene regulation > altered #Bitter taste > heightened #Bitter taste that can occur with infections and #Cancer treatments.
• [1.56] 
  - surgical severance of the sub-diaphragmatic vagus nerve branch prevented these effects of LPS.
• [1.57] [#Cancer] [#IL-1b] 
  - In tissues of the periodontium, monocytes/macrophages, neutrophils, fibroblasts, and mast cells are the primary sources of IL-1β. - these cells synthesize IL-1β in response to activation from the influence of lipopolysaccharide (LPS), the main component of Gram-negative bacteria cell walls. - IL-1β causes osteoclast formation and bone resorption, which leads to local inflammatory changes in the periodontium. - IL-1β activates endothelial cells to produce vascular endothelial growth factor (VEGF) and other proangiogenic factors (e.g., TNF) which provide an inflammatory microenvironment for angiogenesis and tumor progression. - High IL-1β content is associated with tumor invasiveness, migration, and more aggressive tumor phenotype.
• [#IL-1b, #TNF-alfa] - #Fusobacterium nucleatum LPS-activated inflammatory cytokines are include IL-1β, #IL-6, and TNF-α. The chronic inflammatory process leads to the loss of periodontal attachment and tissue damage
• [1.58] [#Metabolic Dysfunction-associated Steatohepatitis, #Metabolic associated fatty liver disease] 
  - The elevated localization of LPS in hepatocytes has been reported in NAFLD and may cause liver inflammation via a TLR4-related pathway. - LPS is a risk factor for inducing hepatic inflammation and NASH. - The upregulation of the LPS-TLR4 pathway leads to NF-κB activation and inflammatory cytokine production, which play key roles in NASH progression and development
• [#Metabolic Dysfunction-associated Steatohepatitis] - #Blautia abundance increased in NASH patients and was positively correlated with LPS levels
• [1.59] [#Short Chain Fatty Acid] 
  - SCFAs, especially #Propionic acid, and #Butyric acid, can inhibit the expressions of cytokines #IL-6 and #IL-12 induced by LPS in human mature dendritic cells.
• - In #Cancer cells, bacterial 16S rRNA was detected mostly in the cytoplasm, whereas LPS staining was associated with both the cytoplasm and the nucleus
• - #Cancer Tissue > the processing of bacterial LPS by macrophages is very slow; therefore, LPS can be found in these cells months after the bacteria were ingested and processed
• [1.61] 
  - #Breast cancer > No evidence of LPS expression within cancer cells. - Instead, LPS immunoreactivity was observed in ducts or immune cells, specifically macrophages.
• [1.62] [#Prevotella copri] [#Branched-chain amino acids] 
  - P. copri can synthesize BCAAs, lipopolysaccharides, and #Tryptophan.
• [1.63] [#Bacteroides stercoris] 
  - Oral gavage of both live and heat-killed B. stercoris into mice could lead to increased lobular inflammation and enhanced expression of genes involved in inflammation activation, which might be explained by the increased serum level of LPS in both groups
• [#Resistant starch] - decreased circulating level of LPS and the lower microbiota functional potential for LPS biosynthesis in human participants after RS intake
• [1.64] [#Parkinson’s Disease] 
  - #Alpha-synuclein overexpression in isolated microglia and peripheral monocytes greatly reduces, in other αSyn overexpressing mice, the cytokine release by these cells after exposure to lipopolysaccharide > absence of substantial central and peripheral inflammation.
• [1.65] [#Akkermansia muciniphila] 
  - the pro-inflammatory nature of a potential pathobiont such as A. muciniphila is determined by the presence or absence of other beneficial bacteria such as #Bifidobacterium spp., modulation of LPS biosynthesis, and immunostimulatory capacity
• - the LPS derived from the feces of mice kept on the #Phytoestrogen-free diet induced significantly higher levels of TNF-α, IL-1β, #IL-6, #IL-12/23, and CXCL1 compared to the LPS derived from feces of mice kept on the #Isoflavone-diet.
• [1.66] [#Cognitive impairment] 
  - TG-treated SAMP8 mice exhibited significant improvement in the parameters of escape latency, distance moved, and annulus crossing index. - #Trigonelline treatment significantly reduces TNFα and IL6 protein levels in SAMP8 mice hippocampus. - it also suppressed LPS-induced TNFα mRNA expression in SH-SY5Y cells. - TG may exert its biological effects through negatively modulating Traf6-mediated NF-κB activation.
• [1.67] [#Hypertension] 
  - #Butyrate significantly reduces the effects of lipopolysaccharide, thereby promoting macrophage 1 polarization and inhibiting macrophage 2 polarization, ultimately leading to a reduction in blood pressure
• [1.68] [#Aggregatibacter actinomycetemcomitans] 
  - The main pathogenic factors attributed to A. actinomycetemcomitans include #Leukotoxin, LPS, surface-associated materials, and various enzymes
• [#Alzheimer’s disease] [#Aggregatibacter actinomycetemcomitans] [#Amyloid-beta] - LPS from serotype B of A. actinomycetemcomitans, > trigger high levels of proinflammatory cytokine production in microglia and an increase the secretion of the Aβ1-42 peptide > AD
• [#Alzheimer’s disease] [#Porphyromonas gingivalis] - intraperitoneally injection of P. gingivalis LPS led to a reduction in the expression of #Neprilysin in the hippocampus > lower levels of #Neprilysin have been associated with increased Aβ accumulation in AD
• [#Porphyromonas gingivalis] - the administration of P gingivalis or its lipopolysaccharide (LPS) induced pro-inflammatory responses and Aβ production in the brain, impairing cognitive performance in Sprague Dawley rats,
• [1.69] 
  - #Butyrate is also able to counteract the pro-inflammatory activity of gut-derived lipopolysaccharides (LPS)
• [#Alcohol Consumption] - Alcohols > alter the GM composition, stimulating the growth of Gram-negative facultative anaerobes producing exotoxins (i.e., lipopolysaccharides, LPS)
• [1.71] [#mRNA vaccine] 
  - Microbiota-derived #Flagellin, #Peptidoglycan, and lipopolysaccharide can act as natural adjuvants to vaccination, recognized by PRRs
• [#Respiratory syncytial virus] - the LPS of #Bacteroides thetaiotaomicron acts as an adjuvant, enhancing the production of #Hepatitis B virus antigen-specific antibodies. - Bacteroides are resident commensals, acting as major polysaccharide degraders in the gut for butyrate production
• [1.72] [#Porphyromonas gingivalis] 
  - P. gingivalis-induced gut dysbiosis suppressed the gene expression of tight junction proteins, causing an increase in serum levels of lipopolysaccharide (LPS)
• [#Porphyromonas gingivalis] - gut microbiota was altered by oral administration of P. gingivalis, the gene expression of tight junction proteins decreased in the gut tissues, LPS levels increased in serum, and larger amounts of bacterial DNA were detected in the liver of mice.
• [1.73] 
  - LPS is a byproduct of Gram-negative gut #Bacteria and is a biomarker of intestinal barrier dysfunction.
• [#Intermittent Hypoxia] - plasma concentrations of LPS in mice exposed to IH remained significantly increased even after 6 weeks of normoxic recovery. - gut dysbiosis still persisted after exposure to normoxia.
• [#Sleep Deprivation] - SF (Sleep Frgamentation) modifies the gut microbiome, leading to an elevation in the #Lachnospiraceae family and a decline in the #Lactobacillaceae family. - The former is associated with intestinal inflammation, whereas the latter acts as a protective barrier. - SF lowers antioxidant capacity and depletes the number of goblet cells and colonocyte proliferation.36 It also intensifies LPS-binding protein circulation levels and stimulates an enhanced inflammatory response.
• - serum LPS concentration is typically low, compromised intestinal barrier integrity can cause an increase in LPS levels. - Elevated LPS levels can activate the Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) pathway, resulting in a systemic inflammatory response that contributes to the development of various diseases.
• [#Obstructive sleep apnea-hypopnea syndrome] - Patients with OSA showed elevated levels of #Proteobacteria, which synthesizes lipopolysaccharide (LPS), associated with systemic inflammation and #Obesity.
• [#Obstructive sleep apnea-hypopnea syndrome] - OSA is a well-established cause of tight junction dysfunction and increased circulating LPS levels.
• [1.74] 
  - #Probiotic #Lactobacillus fermentum CECT5716 can regulate intestinal microecology, increase intestinal density, reduce LPS in serum, restore Th17/Treg balance, and inhibit vascular endothelial #Oxidative stress
• [#Systemic lupus erythematosus] - SLE patients have intestinal flora imbalance. It is characterized by a significant decrease in #Firmicutes/#Bacteroidetes ratio, a decrease in intestinal flora diversity, an increase in the number of Gram-negative bacteria, and an increase in serum lipopolysaccharide (LPS)
• [1.75] 
  - #Equol exhibits blood-brain barrier permeability capability, anti-neuroinflammatory properties, and neuroprotective effects, protecting microglia against lipopolysaccharide (LPS)-induced inflammation and neurotoxins.
• [1.76] [#Peptidoglycan] 
  - TLRs, including TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9, exhibit heightened sensitivity to microbial component alterations, such as peptidoglycans and lipopolysaccharides, distinguishing between physiological colonization and pathogenic presence and actively contributing to initiating inflammatory responses.
• [#Steatohepatitis] - TLR4 in hepatic steatosis > lipopolysaccharide-mediated activation, inducing NF-κB-dependent inflammatory cytokine production.
• [1.77] [#Escherichia coli, #Staphylococcus aureus] 
  - phenolic fractions of #Kale increased DPPH scavengers and decreased pathogenic bacteria, S. aureus and E. coli. - #Kale digesta rich in #Phenolic acids inhibited LPS and TNFɑ-induced intestinal epithelial cell inflammation and upregulated catalase, GSH, and #Superoxide dismutase antioxidant levels against cellular #Oxidative stress
• [1.78] 
  - #Bacteroidetes can reduce the production of intestinal microbial lipopolysaccharides (LPS). - A decreased abundance of #Bacteroidetes may affect the cardiovascular system by increasing the production of LPS, which promotes inflammatory responses.

References Notes