Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections

Ney, None Lisa-Marie; Wipplinger, Maximilian; Grossmann, None Martha; Engert, None Nicole; Wegner, Valentin D; Mosig, Alexander S.

doi:10.1098/rsob.230014

Cited by 61 publications

(19 citation statements)

References 192 publications

(236 reference statements)

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“…While gut microbiota plays a critical role in immune response, gut microbiota alterations were reported to be associated with alteration in Th17 cells [ 29 , 30 ]. Additionally, as mentioned previously, gut microbiota-related metabolites, especially SCFAs, are essential for regulating immune hemostasis [ 31 ]. Whereas, gut dysbiosis and inflammatory gut may lead to lower production of SCFAs [ 32 ], and therefore increase psoriasis risks.…”

Section: Discussionmentioning

confidence: 99%

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study

Zang,

Liu,

Mao

et al. 2023

Dermatol Ther (Heidelb)

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Introduction Previous studies have proposed a possible gut–skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis. Methods With published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane’s Q test, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis. Results By primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR 0.81, P = 0.033) and Prevotella9 (OR 0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR 0.65, P = 0.03), Bacteroidales (OR 0.65, P = 0.03), and Ruminococcaceae UCG002 (OR 0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR 1.22, P = 0.033), Pasteurellaceae (OR 1.22, P = 0.033), Blautia (OR 1.46, P = 0.014), Methanobrevibacter (OR 1.27, P = 0.026), and Eubacterium fissicatena group (OR 1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E. fissicatena group is a possible risk factor for psoriasis (OR 1.22, P = 0.00018). After false discovery rate (FDR) correction, E. fissicatena group remains a risk factor for psoriasis ( P FDR = 0.03798). Conclusion We comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E. fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-023-01007-w.

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Section: Discussionmentioning

confidence: 99%

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study

Zang,

Liu,

Mao

et al. 2023

Dermatol Ther (Heidelb)

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“…First, f_ Ruminococcaceae and f_S24-7 bacteria decreased in both the meropenem and imipenem groups but not in the ertapenem group. The two bacteria can produce short-chain fatty acids (SCFAs) and it has been reported that SCFAs play an important role in the colonization resistance of the gut microbiota against pathogens by coordinating key regulatory factors in the host immune response, regulating intestinal barrier function, or altering the intracellular pH of pathogenic bacteria ( 17 – 20 ). Second, Akkermansia spp.…”

Section: Discussionmentioning

confidence: 99%

The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae

Kuang,

Yang,

Luo

et al. 2023

mSphere

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Gut microbiota plays a crucial role in providing colonization resistance against multi-drug resistant organisms including carbapenem-resistant Klebsiella pneumoniae (CRKP). However, the impact of different carbapenems on intestinal colonization resistance against CRKP remains poorly understood. In this study, we aimed to investigate the effects of three commonly used carbapenems (meropenem, imipenem, and ertapenem) administered at single-day doses, which are typically employed in emergency departments for managing infected patients, on CRKP gut colonization. We conducted experiments in mice by intravenously administering each carbapenem using human-simulated one-day regimens. The composition of the gut microbiota was analyzed using 16S rRNA amplicon sequencing before and after carbapenem administration. Our results revealed that all three carbapenems, when administered at a single-day dose significantly altered the abundance and diversity of the gut microbiota, leading to compromised colonization resistance against CRKP. Notably, the ertapenem and imipenem groups showed an increase in Allobaculum , Bifidobacterium , Enterobacteriaceae , while the meropenem and imipenem groups exhibited a decrease in Ruminococcaceae , S24-7, and Akkermania . Additionally, the Shannon index exhibited a negative correlation with both the number of days of CRKP colonization CFUs and the duration of bacteria shedding. Furthermore, the count of CRKP in mice after ertapenem administration on the first day and the duration of CRKP shedding were significantly lower compared to meropenem and imipenem. Predictive metabolic pathway analysis demonstrated that the three carbapenems similarly affected a range of metabolic pathways of gut microflora, including carbohydrate metabolism and vitamin B. Our findings emphasize that ertapenem, with its relatively narrow spectrum, minimizes perturbations of the gut microbiota and has a relatively less impact on gut colonization resistance against CRKP. IMPORTANCE The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.

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“…SCFAs enter the bloodstream via the intestine, directly influencing the functioning of peripheral tissues and metabolic processes. SCFAs are crucial in regulating gene expression, controlling host metabolic processes (cell proliferation, diversification, and apoptosis), inflammatory reactions, and energy supply ( Abdalkareem Jasim et al, 2022 ; Fillier et al, 2022 ; Rekha et al, 2022 ; Anachad et al, 2023 ; Ney et al, 2023 ). The metabolic responses mediated by SCFA receptors also influence obesity, contributing to AMD ( Tian et al, 2023 ).…”

Section: Gm Composition and Metabolites Influence Amd Developmentmentioning

confidence: 99%

Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota’s influence

Yu,

Liu,

Meng

2024

Front. Pharmacol.

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The pathogenesis of age-related macular degeneration (AMD), a degenerative retinopathy, remains unclear. Administration of anti-vascular endothelial growth factor agents, antioxidants, fundus lasers, photodynamic therapy, and transpupillary warming has proven effective in alleviating symptoms; however, these interventions cannot prevent or reverse AMD. Increasing evidence suggests that AMD risk is linked to changes in the composition, abundance, and diversity of the gut microbiota (GM). Activation of multiple signaling pathways by GM metabolites, including lipopolysaccharides, oxysterols, short-chain fatty acids (SCFAs), and bile acids (BAs), influences retinal physiology. Traditional Chinese medicine (TCM), known for its multi-component and multi-target advantages, can help treat AMD by altering GM composition and regulating the levels of certain substances, such as lipopolysaccharides, reducing oxysterols, and increasing SCFA and BA contents. This review explores the correlation between GM and AMD and interventions for the two to provide new perspectives on treating AMD with TCM.

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Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections

Cited by 61 publications

References 192 publications

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study

The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae

Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota’s influence

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