Bifidobacterium breve-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages

Theranostics, Год журнала: 2024, Номер 14(7), С. 2719 - 2735

Опубликована: Янв. 1, 2024

Aim: To elucidate dynamics and functions in colonic macrophage subsets, their regulation by Bifidobacterium breve (B.breve) its associated metabolites the initiation of colitis-associated colorectal cancer (CAC).Methods: Azoxymethane (AOM) dextran sodium sulfate (DSS) were used to create a CAC model.The tumor-suppressive effect B. variations subsets evaluated.Intestinal macrophages ablated determine role protective effects breve.Efficacious molecules produced identified non-targeted targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.The molecular mechanism was further verified murine bone marrow-derived (BMDMs), derived from human peripheral blood mononuclear cells (hPBMCs), demonstrated mice.Results: alleviated colitis symptoms, delayed tumorigenesis, promoted phenotypic differentiation immature inflammatory into mature homeostatic macrophages.On contrary, ablation intestinal largely annulled breve.Microbial analysis contents revealed enrichment probiotics depletion potential pathogens following supplementation.Moreover, indole-3-lactic acid (ILA) positively correlated with mice highly enriched culture supernatant breve.Also, addition ILA directly AKT phosphorylation restricted pro-inflammatory response BMDMs hPBMCs vitro.The abolished aryl hydrocarbon receptor (AhR) antagonist CH-223191 or inhibitor MK-2206.Furthermore, could protect against tumorigenesis regulating mice; AhR abrogated relieving tumorigenesis.Conclusion: breve-mediated tryptophan metabolism ameliorates precancerous milieu inhibit directing macrophages.

Язык: Английский

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Polysaccharides in fruits: Biological activities, structures, and structure-activity relationships and influencing factors-A review

Food Chemistry, Год журнала: 2024, Номер 451, С. 139408 - 139408

Опубликована: Апрель 23, 2024

Язык: Английский

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Xianlian Jiedu Decoction alleviates colorectal cancer by regulating metabolic profiles, intestinal microbiota and metabolites

Phytomedicine, Год журнала: 2024, Номер 128, С. 155385 - 155385

Опубликована: Янв. 27, 2024

Язык: Английский

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Heavy arch: from inflammatory bowel diseases to metabolic disorders

Gut, Год журнала: 2024, Номер 73(8), С. 1376 - 1387

Опубликована: Май 22, 2024

Background Metabolic disorders and inflammatory bowel diseases (IBD) have captured the globe during Westernisation of lifestyle related dietary habits over last decades. Both disease entities are characterised by complex heterogeneous clinical spectra linked to distinct symptoms organ systems which, on a first glimpse, do not many commonalities in practice. However, experimental studies indicate common backbone mechanisms metabolic gut inflammation, emerging evidence suggests an intricate interplay between IBD. Objective We depict parallels IBD diseases, easily overlooked routine. Design provide overview recent literature discuss implications morbidity patients with for researchers, clinicians healthcare providers. Conclusion The Western diet microbial perturbation serve as fuel inflammation beyond gut. syndrome increasingly affect IBD, expected negative impact both risk complications. This concept implies that tackling obesity pandemic exerts beneficial effects health.

Язык: Английский

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Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in adolescents and young adults (15–39 years): an analysis based on the global burden of disease study 2021

BMC Public Health, Год журнала: 2024, Номер 24(1)

Опубликована: Июль 5, 2024

Abstract Background Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of burden are limited. This study leverages the Global Burden Disease (GBD) 2021 data assess global, regional, national trends major ADs AYAs from 1990 2021. Methods Utilizing Study for individuals aged 15–39 years, we employed a direct method age standardization calculate estimates along with 95% uncertainty intervals (UIs) assessing age-standardized incidence rates (ASIR), prevalence (ASPR), mortality (ASMR) ADs. The analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, Psoriasis. Trends were using Joinpoint regression, providing average annual percentage changes (AAPC) confidence (CIs). Result In 2021, global ASIR, ASPR, ASMR RA (per 100,000 population) 9.46 (95% UI: 5.92 13.54), 104.35 (77.44 137.84), 0.016 (0.013 0.019), respectively. For IBD, corresponding 4.08 (3.07 5.37), 29.55 (23.00 37.83), 0.10 (0.07 0.12). MS exhibited 1.40 (0.93 1.93), 16.05 (12.73 19.75), 0.05 (0.04 0.05), T1DM had 6.63 (3.08 11.84), 245.51 (194.21 307.56), 0.54 (0.47 0.60). Asthma demonstrated 232.22 (132.11 361.24), 2245.51 (1671.05 2917.57), 0.89 (0.77 1.08). Psoriasis showed 55.08 (48.53 61.93) 426.16 (394.12 460.18) ASIR From (AAPC = 0.47, CI: 0.46 0.49), IBD (0.22 [0.12 0.33]), [0.19 0.26]), (0.83 [0.80 0.86]), (0.33 [0.31 0.34]) increasing trends, whereas (-0.96 [-1.03 -0.88]) decreasing trend. ASPR (0.70 [0.68 0.73]), (0.35 [0.32 0.37]), (0.68 [0.66 0.69]), (0.29 [0.27 0.32]) also (-0.20 [-0.27 -0.13]) (-1.25 [-1.31 -1.19]) trends. Notably, estimated (-2.35 [-2.57 -2.12]), (-0.63 [-0.86 -0.41]), (-0.35 [-0.56 -0.14]), (-1.35 [-1.44 -1.26]) in declined. Additionally, varies considerably across continents between 204 countries territories. Conclusion substantial public notable regional disparities incidence, prevalence, rates. Understanding these patterns is essential developing targeted interventions policies mitigate impact this population.

Язык: Английский

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Ternary inulin hydrogel with long-term intestinal retention for simultaneously reversing IBD and its fibrotic complication

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 28, 2024

Excessive accumulation of reactive oxygen and nitrogen species (RONS) dysbiosis intestinal microbiota are pivotal symptoms for inflammatory bowel disease (IBD) its associated complications, such as fibrosis. This research introduces a probiotic inulin hydrogel loaded with polypyrrole (PPy) nanozymes antifibrotic drug pirfenidone (PFD) (PPy/PFD@Inulin gel) designed the concurrent amelioration IBD fibrotic complication. Upon oral administration, gel matrix could extend gastrointestinal residence time PPy PFD, facilitating efficient reduction pro-inflammatory cytokine levels enhancement epithelial barrier repair well suppression fibrosis through sustained RONS scavenging, modulation gut attenuation TGF-β/Smad signaling pathway to inhibit fibroblast proliferation. Notably, PPy/PFD@Inulin demonstrated significant prophylactic therapeutic efficacy in acute chronic colitis induced by dextran sodium sulfate (DSS) mouse models. Thus, engineered ternary offered pioneered paradigm simultaneous reversal fibrosis, single regimen.

Язык: Английский

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The micro(nano)plastics perspective: exploring cancer development and therapy

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 24, 2025

Microplastics, as an emerging environmental pollutant, have received widespread attention for their potential impact on ecosystems and human health. Microplastics are defined plastic particles less than 5 millimeters in diameter can be categorized primary secondary microplastics. Primary microplastics usually originate directly from industrial production, while formed by the degradation of larger items. capable triggering cytotoxicity chronic inflammation, may promote cancer through mechanisms such pro-inflammatory responses, oxidative stress endocrine disruption. In addition, improved bring new perspectives to therapy, studies drug carriers underway, showing high targeting bioavailability. Although current suggest association between certain cancers (e.g., lung, liver, breast cancers), long-term effects specific still need studied. This review aimed at exploring carcinogenicity promising applications therapy provides important directions future research emphasizes multidisciplinary collaboration address this global health challenge.

Язык: Английский

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The combination of Clostridium butyricum and Akkermansia muciniphila mitigates DSS-induced colitis and attenuates colitis-associated tumorigenesis by modulating gut microbiota and reducing CD8 ⁺ T cells in mice

mSystems, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

ABSTRACT The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as Clostridium butyricum (CB) or Akkermansia muciniphila (AKK) have the potential to treat However, research on combined therapeutic effects immunomodulatory mechanisms of CB AKK in treating IBD CRC has never been studied. This study evaluates co-administration DSS/AOM-induced colitis-associated CRC. Our results indicate that compared mono-administration, not only significantly alleviates symptoms weight loss, colon shortening, increased Disease Activity Index mice but also regulates composition effectively suppresses colonic responses. In model, a combination loss markedly reduces infiltration macrophages cytotoxic T lymphocytes (CTLs) colon, thereby regulating anti-tumor immunity inhibiting occurrence inflammation-induced addition, we found probiotic therapy can enhance sensitivity immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), improving efficacy immunotherapy survival rate mice. Furthermore, fecal transplantation showed transplanting feces from treated into other alleviated tumor loads extended their rate. suggests use two probiotics, AKK, alleviate chronic intestinal inflammation inhibit progression may be natural relatively safe method support host’s against cancer. IMPORTANCE administration opposed single strain, holds considerable promise preventing advancement synergistic effect attributed ability this more modulate microbiota, curb reactions, bolster immunotherapeutic approaches, optimize treatment via transplantation.

Язык: Английский

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Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage

Environment International, Год журнала: 2025, Номер 195, С. 109258 - 109258

Опубликована: Янв. 1, 2025

Nanoplastics (NPs) have attracted widespread attention owing to their presence in the body. Recent studies highlighted detrimental effects of NPs on digestive tract. However, no reported an association between exposure and colitis-associated cancer (CAC). An azoxymethane/dextran sodium sulfate-induced CAC model was used, polystyrene nanoparticles (PS-NPs) were selected for long-term exposure. Non-targeted metabolomics 16S rRNA sequencing used detect changes colonic metabolites gut microbes following PS-NPs A lipopolysaccharide (LPS)-treated cell (Caco-2) exposed investigate underlying molecular mechanism. Compared normal control group, mice group exhibited more tumor nodes reactive oxygen species (ROS), higher expression pan-CK Ki-67, severe DNA damage. revealed that altered abundance Allobaculum Lactobacillus, whereas metabolic analysis showed most significant enriched mostly fatty acid metabolism. Experiments LPS intervened Caco-2 cells led lipid peroxidation, oxidative stress, damage Caco-2. Exposure activated phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) signaling pathway both AOM/DSS mouse cellular model. Key proteins involved metabolism downregulated PS-NPs. The significantly inhibited by activation fenofibrate. disturbed induced via PI3K/AKT/mTOR promote progression. Inhibition is a therapeutic controlling PS-NP-induced CAC. Our study provides important reference prevention treatment from perspective environment enhances awareness necessity plastic control.

Язык: Английский

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The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 610 - 610

Опубликована: Янв. 13, 2025

The pentose phosphate pathway (PPP), traditionally recognized for its role in generating nicotinamide adenine dinucleotide (NADPH) and ribose-5-phosphate (R5P), has emerged as a critical metabolic hub with involvements various gastrointestinal (GI) cancers. PPP plays crucial roles the initiation, development, tumor microenvironment (TME) of GI cancers by modulating redox homeostasis providing precursors nucleotide biosynthesis. Targeting enzymes their regulatory axis been potential strategy anti-GI cancer therapies. In this review, we summarize mechanisms enzymes, elucidate relationships between TME's elements, discuss therapeutic targeting

Язык: Английский

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