Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, ...industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 μg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1β, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.
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•Perinatal exposure to EHDPHP led to neuroinflammation and oxidative stress in dams and pups.•EHDPHP upregulated the expressions of inflammation and oxidative stress related biomarkers.•Inulin attenuated EHDPHP-associated oxidative stress and neuroinflammation in both dams and pups.
Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut ...microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.
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•Methamphetamine (METH) exposure induced reproductive toxicity in male mice.•METH exposure caused changes in the gut microbiome and compromised the integrity of the intestinal barrier.•METH exposure altered the testicular transcriptome and metabolic expression profiles.•Fecal microbiota transplantation conveyed similar reproductive damage from METH-treated mice to healthy recipient mice.
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•METH induced hepatotoxicity and enterotoxicity.•Propionate, rather than acetate or butyrate, ameliorates METH-induced hepatotoxicity and enterotoxicity.•Propionate supplementation ...ameliorates intestinal permeability and suppressed the LPS-TLR4-NF-κB pathway, ultimately improving the dysfunction of METH-induced liver and colon.
The abuse of methamphetamine (METH) has emerged as a major public health concern, causing liver and intestinal damage upon exposure. Short chain fatty acids (SCFAs) produced by dietary fiber, including acetate, propionate, and butyrate, have been reported to alleviate various liver toxicities and exhibit distinct physiological effects. However, the role of SCFAs in mitigating METH-induced liver and intestinal damage remains unexplored. This study is designed to elucidate this potential therapeutic effect, by administering either METH or saline via injection to BALB/c mice, supplemented with acetate, propionate, or butyrate in their drinking water. We discovered that propionate demonstrated the most significant effect in mitigating pathological changes, glycogen storage, inflammation, and hepatic function impairments in the liver induced by METH. Propionate supplementation attenuated damage to the intestinal epithelial barrier, restored mucus-secreting cells, inhibited intestinal inflammation, suppressed intestinal hyperpermeability, and reduced lipopolysaccharide (LPS) leakage caused by METH. With the alleviation of LPS endotoxemia, the TLR4/MyD88/NF-κB pathway associated with inflammation in the liver and colon was inhibited. In conclusion, propionate supplementation ameliorated hepatic and colon dysfunction and inflammation resulting from METH exposure through suppression of the TLR4/MyD88/NF-κB pathway.
Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to ...investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1−/−) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.
Gut microbiota involved in Meth-induced colonic inflammation and depression- and anxiety-like behaviors, while SCFAs optimized gut homeostasis and ameliorated mental disorders by modulating the SIGMAR1/BDNF/TRKB pathway. Display omitted
Burn injury has been shown to lead to changes in the composition of the gut microbiome and cause other damage in patients. However, little is known about how the gut microbial community evolves in ...individuals who have recovered from burn injury.
In this study, we established a model of deep partial-thickness burn in mice and collected fecal samples at eight time points (pre-burn, 1, 3, 5, 7, 14, 21, and 28 days post-burn) for 16S rRNA amplification and high-throughput sequencing.
The results of the sequencing were analyzed using measures of alpha diversity, and beta diversity and taxonomy. We observed that the richness of the gut microbiome declined from day 7 post-burn and that the principal component and microbial community structure varied over time. On day 28 after the burn, the microbiome composition largely returned to the pre-burn level, although day 5 was a turning point for change. Some probiotics, such as the Lachnospiraceae_NK4A136_group, decreased in composition after the burn but were restored in the later recovery period. In contrast, Proteobacteria showed an opposite trend, which is known to include potential pathogenic bacteria.
These findings demonstrate gut microbial dysbiosis after burn injury and provide new insights into the burn-related dysbiosis of the gut microbiome and strategies for improving the treatment of burn injury from the perspective of the microbiota.
Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents with sudden onset of chest pain and dyspneic and cardiac dysfunction as a result of extreme physical or emotional stress. The ...sigma-1 receptor (Sigmar1) is a ligand-dependent molecular chaperone that is postulated to be involved in various processes related to cardiovascular disease. However, the role of Sigmar1 in TTS remains unresolved. In this study, we established a mouse model of TTS using wild-type and Sigmar1 knockout mice to investigate the involvement of Sigmar1 in TTS development. Our results revealed that Sigmar1 knockout exacerbated cardiac dysfunction, with a noticeable decrease in ejection fraction (EF) and fractional shortening (FS) compared to the wild-type model. In terms of the gut microbiome, we observed regulation of Firmicutes and Bacteroidetes ratios; suppression of probiotic Lactobacillus growth; and a rise in pathogenic bacterial species, such as Colidextribacter. Metabolomic and transcriptomic analyses further suggested that Sigmar1 plays a role in regulating tryptophan metabolism and several signaling pathways, including MAPK, HIF-1, calcium signaling, and apoptosis pathways, which may be crucial in TTS pathogenesis. These findings offer valuable insight into the function of Sigmar1 in TTS, and this receptor may represent a promising therapeutic target for TTS.
Abstract
While the majority of dry complete and balanced foods for pet animals are extruded, the interaction between ingredient matrix and processing methods and stages are poorly understood. Thus, ...the objective of this study was to determine how the use of plant-based and poultry-based proteins processed under different extrusion condition may affect amino acid digestibility in extruded canine diets using a rooster model. Eight diet formulas were made using chicken (CK), chicken byproduct meal (CM), yellow pea (YP), green lentil (GL), and garbanzo bean (GB) as the primary protein sources. These diets were extruded through a single-screw and a twin-screw extruder. Food samples were collected at various stages of processing (i.e., raw, and after preconditioner, extruder, drier, and coating). Four cecectomized single-comb White Leghorn roosters were used for each diet sample. The roosters were fasted for 26 h and then fed with the treatment diets. The excreta were collected 48 h after feeding. Freeze dried excreta were used to calculate standardized amino acid digestibility (SAAD). For all essential amino acids, a significant interaction (P < 0.05) between diet and processing method was observed. The SAAD of arginine, tryptophan, and methionine were greater than 80% for all diets collected at the end of the extruder. The CK diet supplemented with synthetic taurine and processed through twin-extrusion had 70% to 80% SAAD of histidine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine. Overall, twin-screw extrusion resulted in lower SAAD for all essential amino acids (P < 0.05), except for isoleucine and valine. However, the differences were smaller than 2.5%, and therefore may not negatively impact diet formulation and final product nutrient composition or guaranteed analysis. In addition, the extruded canine diets made with plant-based protein did not have lower amino acid digestibility than those made with animal-based protein.
Abstract
Hydrolyzed protein in companion animal diets has been of public interest because of itsdecreased susceptibility to elicit overreacting immune response and the potentially easier digestion. ...Thus, the objective of this study is to determine the chemical composition, standardized amino acid digestibility, and protein quality of 2 test protein hydrolysates, chicken liver hydrolysate (CLH) and chicken hydrolysate (CH), compared with a traditional chicken meal low ash (CM) in extruded canine diets. Five treatment diets were formulated to have similar ingredient compositions except for the main protein source, 1) CONd: CM diet; 2) 5%CLHd: 5% substitution of CLH of CM diet; 3) CLHd: CLH diet; 4) 5%CHd: 5% substitution of CH of CM diet; 5) CHd: CH diet. A precision-fed rooster assay using cecectomized roosters (n=4/treatment) was conducted to determine the standardized amino acid ileal digestibility and Digestible Indispensable Amino Acid Score (DIAAS) like values for the 3 protein ingredients and 5 extruded diets. The standardized ileal digestibility for the 10 indispensable amino acids was all equal or greatere than 80% in all protein sources and treatment diets. Tryptophan digestibility in 5%CLHd was less than CLHd (P < 0.05) but no difference was seen when compared with the other diets (P > 0.05). The DIAAS-like values of the diets according to AAFCO nutrient profile showed that tryptophan was the first limiting amino acid for CONd, 5%CLHd, and 5%CHd; the diets containing only protein hydrolysates had no limiting amino acid as their DIAAS-like values were greater than 100%. The DIAAS-like values were less in CONd (95.6%), 5%CLHd (94.9%), and 5%CHd (96.2%) compared with CLHd (104.5%) and CHd (116.9%) (P < 0.05). In conclusion, all test protein sources were well digested; however, substituting CM with protein hydrolysate could increase protein quality in canine extruded diets.
Abstract
Research on protein hydrolysates has observed various properties and functionalities of these ingredients depending on the type of hydrolysate. The objective of this study was to evaluate ...the effects of hydrolyzed chicken protein that was incorporated into diets on digestibility, gut health, skin and coat health, oxidative stress, and inflammation in healthy adult dogs. Five complete and balanced treatment diets were manufactured: 1) CONd: chicken meal diet; 2) 5% CLHd: 5% substitution of chicken liver hydrolysate of chicken meal diet; 3) CLHd: chicken liver hydrolysate diet; 4) 5% CHd: 5% substitution of chicken hydrolysate of chicken meal diet; and 5) CHd: chicken hydrolysate diet. A 5×5 Latin square design was used which included 10 neutered adult beagles. Each of the 5 periods consisted of a 7-d washout time and a 28-d treatment period. All diets were well accepted by the dogs. There was greater (P < 0.05) fecal butyrate (226.8 μmol/g DMB) concentration as well as decreasedr isovalerate (6.8 μmol/g DMB), 4-ethylphenol (1.4 μmol/g DMB), and indole (0.7 μmol/g DMB) in dogs fed CLHd than CONd (149.3, 10.8, 2.5, and 1.5 μmol/g DMB, respectively). Doges fed CHd had greater (P < 0.05) fecal immunoglobulin A concentration (2.86 mg/g) when compared with CLHd (0.91 mg/g); however, both groups were comparable to the control. There was no difference among groups in serum cytokine concentrations, serum oxidative stress biomarkers, or skin and coat health analyses (P > 0.05). In conclusion, chicken protein hydrolysate could be incorporated into canine extruded diets as a comparable source of protein to traditional chicken meal. The test chicken protein hydrolysates may have potential to support gut health by modulating immune response and fermentative activity; however, more research is needed to confirm the effect.
Research on protein hydrolysates has observed various properties and functionalities on ingredients depending on the type of hydrolysate. The objective of this study was to evaluate the effects of ...hydrolyzed chicken protein that was incorporated into diets on digestibility, gut health, skin and coat health, oxidative stress, and intestinal inflammation markers in healthy adult dogs. Five complete and balanced diets were manufactured: (1) CONd: 25% chicken meal diet; (2) 5% CLHd: 5% chicken liver and heart hydrolysate plus 20% chicken meal diet; (3) CLHd: 25% chicken liver and heart hydrolysate diet; (4) 5% CHd: 5% chicken hydrolysate plus 20% chicken meal diet; (5) CHd: 25% chicken hydrolysate diet. A replicated 5 × 5 Latin square design was used which included 10 neutered adult Beagles. Each of the 5 periods consisted of a 7-d washout time and a 28-d treatment period. All diets were well accepted by the dogs. Fecal butyrate concentration was higher while fecal isovalerate and total phenol/indole were lower in dogs fed CLHd than CONd (P < 0.05). Dogs fed CHd had higher fecal immunoglobulin A concentration when compared with CLHd (P < 0.05); however, both groups were comparable to the CONd. There was no difference among groups in serum cytokine concentrations, serum oxidative stress biomarkers, or skin and coat health analyses (P > 0.05). Fecal microbiota was shifted by CLHd with higher abundance in Ruminococcus gauvreauii group as well as lower Clostridium sensu stricto 1, Sutterella, Fusobacterium, and Bacteroides when compared with CONd (P < 0.05). There was also a difference in beta diversity of fecal microbiota between CLHd and CHd (P < 0.05). In conclusion, chicken protein hydrolysate could be incorporated into canine extruded diets as a comparable source of protein to traditional chicken meal. The test chicken protein hydrolysates showed the potential to support gut health by modulating immune response and microbiota; however, functional properties of protein hydrolysates are dependent on inclusion level and source.
