Altered Expression of Antimicrobial Peptides in the Upper Gastrointestinal Tract of Patients with Diabetes Mellitus

Linn, Oliver; Menges, Bernhard; Lammert, Frank; Weber, Susanne N.; Krawczyk, Marcin

doi:10.3390/nu15030754

Cited by 7 publications

(3 citation statements)

References 51 publications

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“…In agreement with improved liver function, we were able to show that oral administration of either HD5 1–9 or hBD2 attenuated diet-induced glucose intolerance in mice fed a WSDF, resulting in a lowering of blood glucose curves and a reduction in the AUC. Since type 2 diabetes mellitus (T2DM) and decreased HDP expression in the upper small intestinal tract and saliva was found to be associated in human studies [ 52 , 53 ], we were interested to quantify the effects of HD5 1–9 or hBD2 on glucose metabolism. Although we did not observe any effects on fasting blood glucose levels, HD5 1–9 and hBD2 improved blood glucose curves at 30 min after glucose administration in CDF- and WSDF-fed mice.…”

Section: Discussionmentioning

confidence: 99%

Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet

Filipe Rosa,

Rings,

Stolzer

et al. 2023

IJMS

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Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice were fed a WSD or a control diet (CD) ± fructose (F) for 18 weeks. In week 13, mice were randomly divided into three intervention groups, receiving defensin fragment HD51–9, full-length hBD2, or bovine serum albumin (BSA)-control for six weeks. Subsequently, parameters of hepatic steatosis, glucose metabolism, and gut barrier function were assessed. WSDF increased body weight and hepatic steatosis (p < 0.01) compared to CD-fed mice, whereas peptide intervention decreased liver fat (p < 0.05) and number of hepatic lipid droplets (p < 0.01) compared to BSA-control. In addition, both peptides attenuated glucose intolerance by reducing blood glucose curves in WSDF-fed mice. Evaluation of gut barrier function revealed that HD51–9 and hBD2 improve intestinal integrity by upregulating tight junction and mucin expression. Moreover, peptide treatment restored ileal host defense peptides (HDP) expression, likely by modulating the Wnt, Myd88, p38, and Jak/STAT pathways. These findings strongly suggest that α- and β-defensin treatment improve hepatic steatosis, glucose metabolism, and gut barrier function.

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Section: Discussionmentioning

confidence: 99%

Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet

Filipe Rosa,

Rings,

Stolzer

et al. 2023

IJMS

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show abstract

“…Lin et al determined that hBD-1, human beta defensin 1, was reduced in the gastric corpus in the diabetic metabolic state. Given this information, the induction of AMP expression may help resolve issues involved in intestinal barrier deficiency [ 58 ].…”

Section: Amps and Their Relationships With Human Diseasesmentioning

confidence: 99%

Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology

et al. 2023

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Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used to improve AMP bioavailability, permeation across barriers, and/or protection against degradation. In addition, machine learning has been investigated due to its time-saving and cost-effective algorithms to predict AMPs. There are numerous databases available to train machine learning models. In this review, we focus on nanotechnology approaches for AMP delivery and advances in AMP design via machine learning. The AMP sources, classification, structures, antimicrobial mechanisms, their role in diseases, peptide engineering technologies, currently available databases, and machine learning techniques used to predict AMPs with minimal toxicity are discussed in detail.

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“…However, the small molecular weight, cationic nature, and sensitivity to salt and pH of AMPs make them prone to hydrolysis and inactivation, resulting in high production costs and difficulties in preservation [27]. Therefore, it may be more effective to enhance the levels of endogenous AMPs by utilizing the inherent regulatory mechanisms of their expression as an immunotherapeutic approach against tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells

Chen,

Han,

Zhang

et al. 2024

IJMS

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Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human β-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

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Altered Expression of Antimicrobial Peptides in the Upper Gastrointestinal Tract of Patients with Diabetes Mellitus

Cited by 7 publications

References 51 publications

Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet

Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet

Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells

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