Exposure of Caenorhabditis elegans to Dietary Nε-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products

The impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free AGE adducts and transport of glycated di-tripeptides by the peptide transporter 1 (PEPT-1), are not compatible with certain pathophysiological processes described. To get new insight into the intestinal absorption pathways and the pathophysiological mechanisms of dAGEs, we initiated an in vivo study with a so-called simple animal model with a complete digestive tract, Caenorhabditis elegans. Dietary bacteria were chemically modified with glyoxylic acid to mainly produce Nε-carboxymethyllysine (CML) and used to feed the worms. We performed different immunotechniques using an anti-CML antibody for the relative quantification of ingested CML and localization of this AGE in the worms’ intestine. The relative expression of genes encoding different biological processes such as response to stresses and intestinal digestion were determined. The physiological development of the worms was verified. All the results were compared with those obtained with the control bacteria. The results revealed a new route for the intestinal absorption of dietary CML (dCML), endocytosis, which could be mediated by scavenger receptors. The exposure of worms to dCML induced a reproductive defect and a transcriptional response reflecting oxidative, carbonyl and protein folding stresses. These data, in particular the demonstration of endocytosis of dCML by enterocytes, open up new perspectives to better characterize the pathophysiological mechanisms of dAGEs.

Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway

Background Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear. Methods In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16 s rRNA microbiome and metabolomic analyses. Results The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients’ clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16 s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-glutamyl-L-glutamic acid, Glycerophosphocholine, et al., after FMT. Compared with baseline, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L-Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L-Arginine and L-Threonine were also involved in the pathway. A large amount of Na + was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle. Conclusions Therefore, we speculated that FMT changed the patients’ gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC. Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.

Effect of Fecal Microbiota Transplantation in Patients With Slow Transit Constipation and the Relative Mechanisms Based On the Protein Digestion and Absorption Pathway

Background: Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear. Methods: In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16s rRNA microbiome and metabolomic analyses. Results: The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients’ clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-Glutamyl-L-glutamic acid, Glycerophosphocholine, et al, after FMT. Meanwhile, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L‐Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L‐Arginine and L-Threonine were also involved in the pathway. A large amount of Na+ was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle. Conclusions: Therefore, we speculated that FMT changed the patients’ gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC.Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.

Risk assessment of metals from shallow groundwater in Lianhuashan District, China

The present study was conducted to investigate trace metal (Fe, Mn, Cd, Pb, Zn, Cu, Al, As, Se, Hg, Sr, Ba, Li, Co, B, Ni, Ag, Mo and Cr) concentrations of drinking water samples in Lianhuashan District, China. Furthermore, the study aimed to ascertain carcinogenic and non-carcinogenic health risks of metals by ingestion and dermal absorption pathways to the local residents. Metal concentrations were compared with permissible limits set by the Chinese Standards, USEPA and WHO. The average concentrations of the analyzed elements are in the order of Fe > Sr > Mn > Al > Ba > Mo > Zn > B > Li > Pb > Cr > Ni > Cu > Ag > Co > As > Se > Cd > Hg. The results indicate that the concentrations of Cd, Zn, Cu, Ni, Se, Hg, Ba and Cr were lower than their respective permissible limits, whereas the concentrations of Fe, Mn, Pb, Al, As and Mo at some sampling sites exceeded the permissible limits. The total hazard index (HQtotal) of the metals (Cd, Zn, Cu, Al, Se, Hg, Sr, Ba, B, Ni, Ag, Cr) calculated through ingestion and dermal absorption pathways for adults and children were found to be lower than unity, indicating that the metals would not pose any adverse effect and non-carcinogenic health risk to the habitants. The results of carcinogenic risk assessment indicate that the Excess Lifetime Cancer Risk (ingestion and dermal exposure pathways) of metals exposure was in accordance to the acceptable lifetime risks for carcinogens in drinking water (10−6–10−4). Both non-carcinogenic and carcinogenic risks were mainly attributed to the ingestion pathways.

A Review of a Class of Emerging Contaminants: The Classification, Distribution, Intensity of Consumption, Synthesis Routes, Environmental Effects and Expectation of Pollution Abatement to Organophosphate Flame Retardants (OPFRs)

Organophosphate flame retardants (OPFRs) have been detected in various environmental matrices and have been identified as emerging contaminants (EC). Given the adverse influence of OPFRs, many researchers have focused on the absorption, bioaccumulation, metabolism, and internal exposure processes of OPFRs in animals and humans. This paper first reviews the evolution of various types of flame retardants (FRs) and the environmental pollution of OPFRs, the different absorption pathways of OPFRs by animals and humans (such as inhalation, ingestion, skin absorption and absorption), and then summarizes the environmental impacts of OPFRs, including their biological toxicity, bioaccumulation, persistence, migration, endocrine disruption and carcinogenicity. Based on limited available data and results, this study also summarizes the bioaccumulation and biomagnification potential of OPFRs in different types of biological and food nets. In addition, a new governance idea for the replacement of existing OPFRs from the source is proposed, seeking environmentally friendly alternatives to OPFRs in order to provide new ideas and theoretical guidance for the removal of OPFRs.