White feces syndrome (WFS) is a multifactorial disease that affects global shrimp production. The diagnostic approach to identify WFS involves traditional and molecular scientific methods by examining histopathology, bioassays, PCR (polymerase chain reaction), and calorimetric estimation. The pathogenesis of WFS is closely associated with Vibrio spp., intestinal microbiota (IM) dysbiosis, and Enterocytozoon hepatopenaei (EHP). It also has caused over 10-15 % loss in the aquaculture industry and is also known to cause retardation, lethargy and slowly leading to high mortality in shrimp farms. Therefore, it is necessary to understand the molecular mechanisms processed under the association of IM dysbiosis, Vibrio spp., and EHP to analyze the impact of disease on the innate immune system of shrimp. However, only very few reviews have described the molecular pathways involved in WFS. Hence, this review aims to elucidate an in-depth analysis of molecular pathways involved in the innate immune system of shrimp and their response to pathogens. The analysis and understanding of the impact of shrimp\'s innate immune system on WFS would help in developing treatments to prevent the spread of disease, thereby improving the economic condition of shrimp farms worldwide.

To establish and evaluate an intestinal microbiota dysbiosis-induced obesity mouse model. 50 C57BL/6 J male healthy mice were randomly divided into an obesity model group and the control group. The body weight, body length, and Lee\'s index of the two groups of mice at week 1 and week 10 were compared. Serum glucose (GLU), total cholesterol (TC) and triglyceride (TG) were measured by enzyme-labeled colorimetric methods. Illumina HiSeq 16S rDNA high-throughput sequencing technology was used to characterize intestinal microbiota in feces. The success rate of model establishment in obese mice was 52%. The body weight, body length, Lee\'s index, and abdominal fat (wet weight) in the obese model group were all higher than those in the control group, and the differences were statistically significant (P < 0.01). Serum GLU and TC levels in the obesity model group were higher than those in the control group (P < 0.05), and there was no difference in TG levels between the two groups (P > 0.05). The control group contained more abundant intestinal microbiota phyla and genera than did the obesity model group; the differences between the two groups were significant (FDR ≤ 0.05, P ≤ 0.05). Intestinal microbiota dysbiosis can be used to generate an obesity model in mice.

The premise that pathogen colonized microplastics (MPs) can promote the spread of pathogens has been widely recognized, however, their role in the colonization of pathogens in a host intestine has not been fully elucidated. Here, we investigated the effect of polystyrene MPs (PS-MPs) on the colonization levels of Aeromonas veronii, a typical aquatic pathogen, in the loach (Misgurnus anguillicaudatus) intestine. Multiple types of MPs were observed to promote the intestinal colonization of A. veronii, among which PS-MPs exhibited the most significant stimulating effect (67.18% increase in A. veronii colonization). PS-MPs inflicted serious damage to the intestinal tracts of loaches and induced intestinal microbiota dysbiosis. The abundance of certain intestinal bacteria with resistance against A. veronii colonization decreased, with Lactococcus sp. showing the strongest colonization resistance (73.64% decline in A. veronii colonization). Fecal microbiota transplantation was performed, which revealed that PS-MPs induced intestinal microbiota dysbiosis was responsible for the increased colonization of A. veronii in the intestine. It was determined that PS-MPs reshaped the intestinal microbiota community to attenuate the colonization resistance against A. veronii colonization, resulting in an elevated intestinal colonization levels of A. veronii.

Raoultella ornithinolytica is an Enterobacteriaceae bacterium that can infect both humans and animals, while luteolin-7-O-glucoside (IOG) is a flavonoid that has broad effects on the intestinal microbiota of healthy animals. However, current studies lack sufficient data on intestinal microbiota dysbiosis and drug resistance transmission caused by R. ornithinolytica and the possible role of IOG. In this study, BALB/c mice were infected with R. ornithinolytica carrying blaNDM-1 gene and treated with IOG (3 mg/kg·d and 6 mg/kg·d) to analyze the diversity of intestinal microbiota and the transfer of blaNDM-1 between bacteria. The findings indicated that R. ornithinolytica B1645-1 exhibited a significant ability to enhance the Firmicutes/Bacteroidota ratio and increase the relative abundance of Lactobacillus and Bacillus after 48 h, where as 6 mg/kg·d IOG had an opposite effect. Moreover, R. ornithinolytica B1645-1 facilitated the emergence of drug-resistant bacteria and promoted blaNDM-1 gene transfer in Enterococcus, Escherichia, Klebsiella, Acinetobacter, Bacillus, Brevibacterium, and Lactobacillus. Enterococcus was the predominant genus at 48 h. Surprisingly, 6 mg/kg·d IOG significantly inhibited the production of drug-resistant bacteria and promoted blaNDM-1 gene transfer from Enterococcus to Lactobacillus at 144 h. However, the role of Lactobacillus as a recipient for drug-resistant genes should be of more concern.

The antidiabetic pharmaceutical metformin (MET) is largely unmetabolized by the human body. Its residues are readily detectable in various aquatic environments and may have adverse impacts on the growth and survival of aquatic species. To date, its toxicological effects have scarcely been explored in non-fish species. Here, we exposed the tadpoles of black-spotted pond frog (Pelophylax nigromaculatus) to different concentrations (0, 1, 10 and 100 μg/L) of MET for 30 days and measured the body size, intestinal microbiota and metabolites to evaluate potential effects of MET exposure in amphibian larvae. MET exposure did not affect the growth and intestinal microbial diversity of tadpoles. However, intestinal microbial composition changed significantly, with some pathogenic bacteria (e.g., bacterial genera Salmonella, Comamonas, Stenotrophomonas, Trichococcus) increasing and some beneficial bacteria (e.g., Blautia, Prevotella) decreasing in MET-exposed tadpoles. The levels of some intestinal metabolites associated with growth and immune performance also changed significantly following MET exposure. Overall, our results indicated that exposure to MET, even at environmentally relevant concentrations, would cause intestinal microbiota dysbiosis and metabolite alteration, thereby influencing the health status of non-target aquatic organisms, such as amphibians.

Antibiotic selectivity and bacterial resistance are critical global public health issues. We constructed a multi-class machine learning model to study antibiotic effects on human intestinal microbiota abundance and identified key features. Binding energies of β-lactam antibiotics with Escherichia coli PBP3 mutant protein were calculated, and a 2D-QSAR model for bacterial resistance was established. Sensitivity analysis identified key features affecting bacterial resistance. By coupling key features from the machine learning model and 2D-QSAR model, we designed ten flucloxacillin (FLU) substitutes that improved intestinal microbiota tolerance and reduced antibiotic bacterial resistance. Concurrently, the substitutes exhibited superior degradability in soil, aquatic environments, and under photolytic conditions, coupled with a reduced environmental toxicity compared to the FLU. Evaluations under combined medication revealed significant improvements in functionality and bacterial resistance for 80% of FLU substitutes, with 50% showing more than a twofold increase. Mechanistic analysis demonstrated enhanced binding to target proteins and increased biodegradability for FLU substitutes due to more concentrated surface charges. Reduced solvent hindrance and increased cell membrane permeability of FLU substitutes, mainly due to enhanced interactions with phospholipid bilayers, contributed to their functional selectivity. This study aims to address poor antibiotic selectivity and strong bacterial resistance, providing guidance for designing antibiotic substitutes.

Cardiac allograft rejection remains a major factor limiting long-term engraftment after transplantation. A novel phosphoinositide 3-kinase (PI3K)/mTOR dual inhibitor, BEZ235, prolonged cardiac allograft survival by effectively suppressing activation of the PI3K/serine/threonine kinase (AKT)/mTOR pathway. However, long-term usage of pharmacological immunosuppressant drugs can cause intestinal microbiota dysbiosis. We established mouse models of allogeneic heterotopic heart transplantation with different treatments. Fecal samples were collected and subjected to 16S rRNA sequencing and targeted fecal metabolomic analysis. Graft samples were taken for immune cell detection by flow cytometry. Inflammatory cytokines in serum were quantified by enzyme-linked immunosorbent assay (ELISA). Compared to single-target approaches (IC-87114 and rapamycin), BEZ235 more efficiently prolongs cardiac transplant survival. Interestingly, BEZ235 reduces the diversity and abundance of the intestinal microbiota community. We demonstrated that Lactobacillus rhamnosus HN001 rescues the intestinal microbiota imbalance induced by BEZ235. IMPORTANCE Our data confirmed that the combination of BEZ235 and Lactobacillus rhamnosus HN001 significantly prolongs cardiac transplant survival. A main metabolic product of Lactobacillus rhamnosus HN001, propionic acid (PA), enriches regulatory T (Treg) cells and serves as a potent immunomodulatory supplement to BEZ235. Our study provides a novel and efficient therapeutic strategy for transplant recipients.

Tartrazine (TZ) is an azo dye widely used in foods, cosmetics, beverages, textile, and leather. In recent years, there are reports on detecting azo dyes in the aquatic environment, so the impact of these compounds on aquatic organisms could not be ignored. In this study, we aimed to evaluate the adverse effects of TZ exposure on teleosts\' embryo development and juvenile\'s health by using crucian carp (Carassius carassius) as the experimental fish. The results showed that embryos exposed to TZ (0.19, 0.76 and 1.5 mM) exhibited a deformity, delayed egg resorption and decreased fertilization and hatching rate. When the juvenile fish were exposed to TZ at a level higher than those present in water for 30 days caused severe histopathological damages of the gill, intestine, kidney and liver. Antioxidant enzymes (CAT, SOD and GSH-Px) activities in the gill, intestine and liver, exhibited a decreasing trend after TZ exposure, while MDA contents elevated. TZ exposure also resulted in the upregulation of pro-inflammatory cytokines (il1 and il6), lysozymes (lyz), complement component 3 (c3), and β-defensin 3 (defb3). In addition, TZ exposure also affected the intestinal microbiota structure. In summary, the data in the present study indicated that TZ exposure  reduce the embryo fertilization and hatching rate; cause histopathological damage of tissues, trigger oxidative stress, innate immune disorders and dysbiosis of gut microbiota in juvenile crucian carp. Therefore, it is necessary to be informed about the hazards of TZ exposure and the discharge of the dye into waters should be strictly administrated to prevent environmental pollution.

Chemotherapy-induced intestinal mucositis, a painful debilitating condition affecting up to 40-100% of patients undergoing chemotherapy, can reduce the patients\' quality of life, add health care costs and even postpone cancer treatment. In recent years, the relationships between intestinal microbiota dysbiosis and mucositis have drawn much attention in mucositis research. Chemotherapy can shape intestinal microbiota, which, in turn, can aggravate the mucositis through toll-like receptor (TLR) signaling pathways, leading to an increased expression of inflammatory mediators and elevated epithelial cell apoptosis but decreased epithelial cell differentiation and mucosal regeneration. This review summarizes relevant studies related to the relationships of mucositis with chemotherapy regimens, microbiota, TLRs, inflammatory mediators, and intestinal homeostasis, aiming to explore how gut microbiota affects the pathogenesis of mucositis and provides potential new strategies for mucositis alleviation and treatment and development of new therapies.

Cigarette smoke is a representative source of toxic chemical exposures to humans, and the adverse consequences of cigarette smoking are mediated by its effect on both neuronal and immune-inflammatory systems. Cigarette smoking also is a major risk factor for intestinal disorders, such as Crohn\'s disease and peptic ulcer. On the other hand, cigarette smoking is protective against developing ulcerative colitis. The effects of cigarette smoking on intestinal disorders include changes in intestinal irrigation and microbiome, increases in permeability of the mucosa, and impaired mucosal immune responses. However, the underlying mechanism linking cigarette smoking with intestinal microbiota dysbiosis is largely unknown. In this communication, we first review the current knowledge about the mechanistic interaction between cigarette smoke and intestinal microbiota dysbiosis, which include the likely actions of nicotine, aldehydes, polycyclic aromatic hydrocarbons, heavy metals, volatile organic compounds and toxic gases, and then reveal the potential mechanisms of the lung-gut cross talk and skin-gut cross talk in regulating the balance of intestinal microbiota and the interrelation of intestinal microbiota dysbiosis and systemic disorders.