Futoquinol improves Aß25-35-induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota.

Futoquinol (Fut) is a compound extracted from Piper kadsura that has a nerve cell protection effect. However, it is unclear whether Fut has protective effects in Alzheimer's disease (AD). In this study, we aimed to explore the therapeutic effect of Fut in AD and its underlying mechanism. UPLC-MS/MS method was performed to quantify Fut in the hippocampus of mice brain. The cognition ability, neuronal and mitochondria damage, and levels of Aß1-42, Aß1-40, p-Tau, oxidative stress, apoptosis, immune cells, and inflammatory factors were measured in Aß25-35-induced mice. The content of bacterial meta-geometry was predicted in the microbial composition based on 16S rDNA. The protein levels of HK II, p-p38MAPK, and p38MAPK were detected. PC-12 cells were cultured in vitro, and glucose was added to activate glycolysis to further explore the mechanism of action of Fut intervention in AD. Fut improved the memory and learning ability of Aß25-35 mice, and reduced neuronal damage and the deposition of Aß and Tau proteins. Moreover, Fut reduced mitochondrial damage, the levels of oxidative stress, apoptosis, and inflammatory factors. Fut significantly inhibited the expression of HK II and p-p38MAPK proteins. The in vitro experiment showed that p38MAPK was activated and Fut action inhibited after adding 10 mM glucose. Fut might inhibit the activation of p38MAPK through the glycolysis pathway, thereby reducing oxidative stress, apoptosis, and inflammatory factors and improving Aß25-35-induced memory impairment in mice. These data provide pharmacological rationale for Fut in the treatment of AD.

Prenatal caffeine exposure induces autism-like behaviors in offspring under a high-fat diet via the gut microbiota-IL-17A-brain axis.

Prenatal caffeine exposure (PCE) is a significant contributor to intrauterine growth retardation (IUGR) in offspring, which has been linked to an increased susceptibility to autism spectrum disorder (ASD) later in life. Additionally, a high-fat diet (HFD) has been shown to exacerbate ASD-like behaviors, but the underlying mechanisms remain unclear. In this study, we first noted in the rat model of IUGR induced by PCE that male PCE offspring exhibited typical ASD-like behaviors post-birth, in contrast to their female counterparts. The female PCE offspring demonstrated only reduced abilities in free exploration and spatial memory. Importantly, both male and female PCE offspring displayed ASD-like behaviors when exposed to HFD. We further observed that PCE + HFD offspring exhibited damaged intestinal mucus barriers and disturbed gut microbiota, resulting in an increased abundance of Escherichia coli (E. coli). The induced differentiation of colonic Th17 cells by E. coli led to an increased secretion of IL-17A, which entered the hippocampus through peripheral circulation and caused synaptic damage in hippocampal neurons, ultimately resulting in ASD development. Our strain transplantation experiment suggested that E. coli-mediated increase of IL-17A may be the core mechanism of ASD with a fetal origin. In conclusion, PCE and HFD are potential risk factors for ASD, and E. coli-mediated IL-17A may play a crucial role in fetal-originated ASD through the gut-brain axis.

Responses of soil and collembolan (Folsomia candida) gut microbiomes to 6PPD-Q pollution.

The potential risk of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) to soil organisms remains poorly understood. Here we showed that 6PPD-Q pollution inhibited the survival of collembolans (Folsomia candida) with the chronic median lethal concentration (LC50) of 16.31 µg kg-1 in a 28-day soil culture. The microbe-microbe interactions between abundant taxa in soil and collembolan gut helped alleviate the negative impact of 6PPD-Q on soil microbial community, while rare taxa contributed to maintaining microbial network complexity and stability under 6PPD-Q stresses. Gammaproteobacteria, Alphaproteobacteria and Actinobacteria in the gut of both adult and juvenile collembolans were identified as potential indicators for 6PPD-Q exposure. Such responses were accompanied by increases in the relative abundances of genes involved in nutrient cycles and their interactions between soil and collembolan gut microbiomes, which enhanced nitrogen and carbon turnover in 6PPD-Q polluted soil, potentially alleviating the stresses caused by 6PPD-Q. Overall, this study sheds new light on the toxicity of 6PPD-Q to soil organisms and links 6PPD-Q stresses to microbial responses and soil functions, thus highlighting the urgency of assessing its potential risk to the terrestrial ecosystem.

Artificial Sweetener Enhances the Spread of Antibiotic Resistance Genes During Anaerobic Digestion.

Artificial sweeteners have been frequently detected in the feedstocks of anaerobic digestion. As these sweeteners can lead to the shift of anaerobic microbiota in the gut similar to that caused by antibiotics, we hypothesize that they may have an antibiotic-like impact on antibiotic resistance genes (ARGs) in anaerobic digestion. However, current understanding on this topic is scarce. This investigation aimed to examine the potential impact of acesulfame, a typical artificial sweetener, on ARGs in anaerobic digestion by using metagenomics sequencing and qPCR. It was found that acesulfame increased the number of detected ARG classes and the abundance of ARGs during anaerobic digestion. The abundance of typical mobile genetic elements (MGEs) and the number of potential hosts of ARGs also increased under acesulfame exposure, suggesting the enhanced potential of horizontal gene transfer of ARGs, which was further confirmed by the correlation analysis between absolute abundances of the targeted ARGs and MGEs. The increased horizontal dissemination of ARGs may be associated with the SOS response induced by the increased ROS production, and the increased cellular membrane permeability. These findings indicate that artificial sweeteners may accelerate ARG spread through digestate disposal, thus corresponding strategies should be considered to prevent potential risks in practice.

Transgenic mice lacking FGF15/19-SHP phosphorylation display altered bile acids and gut bacteria, promoting nonalcoholic fatty liver disease.

Dysregulated bile acid (BA)/lipid metabolism and gut bacteria dysbiosis are tightly associated with the development of obesity and non-alcoholic fatty liver disease (NAFLD). The orphan nuclear receptor, Small Heterodimer Partner (SHP/NR0B2), is a key regulator of BA/lipid metabolism, and its gene-regulating function is markedly enhanced by phosphorylation at Thr-58 mediated by a gut hormone, fibroblast growth factor-15/19 (FGF15/19). To investigate the role of this phosphorylation in whole-body energy metabolism, we generated transgenic SHP-T58A knock-in mice. Compared with wild-type (WT) mice, the phosphorylation-defective SHP-T58A mice gained weight more rapidly with decreased energy expenditure and increased lipid/BA levels. This obesity-prone phenotype was associated with the upregulation of lipid/BA synthesis genes and downregulation of lipophagy/ß-oxidation genes. Mechanistically, defective SHP phosphorylation selectively impaired its interaction with LRH-1, resulting in de-repression of SHP/LRH-1 target BA/lipid synthesis genes. Remarkably, BA composition and selective gut bacteria which are known to impact obesity, were also altered in these mice. Upon feeding a high-fat diet, fatty liver developed more severely in SHP-T58A mice compared to WT mice. Treatment with antibiotics substantially improved the fatty liver phenotypes in both groups but had greater effects in the T58A mice so that the difference between the groups was largely eliminated. These results demonstrate that defective phosphorylation at a single nuclear receptor residue can impact whole-body energy metabolism by altering BA/lipid metabolism and gut bacteria, promoting complex metabolic disorders like NAFLD. Since posttranslational modifications generally act in gene- and context-specific manners, the FGF15/19-SHP phosphorylation axis may allow more targeted therapy for NAFLD.

Bacillus coagulans (Weizmannia coagulans) XY2 attenuates Cu-induced oxidative stress via DAF-16/FoxO and SKN-1/Nrf2 pathways and gut microbiota regulation.

Copper (Cu) pollution has become a serious environmental problem especially in recent decades. In this study, the mechanisms of Bacillus coagulans (Weizmannia coagulans) XY2 against Cu-induced oxidative stress were explored through a dual model. In mice, Cu disturbed microbial community structure, revealing an increased level of Enterorhabdus abundance and decreased levels of Intestinimonas, Faecalibaculu, Ruminococcaceae and Coriobacteriaceae_UCG-002 abundance. Meanwhile, B. coagulans (W. coagulans) XY2 intervention reversed this trend along with alleviated Cu-induced metabolic disturbances by increasing levels of hypotaurine and L-glutamate and declining levels of phosphatidylcholine and phosphatidylethanolamine. In Caenorhabditis elegans, nuclear translocation of DAF-16 and SKN-1 was inhibited by Cu, which in turn suppressed antioxidant-related enzymes activities. XY2 mitigated biotoxicity associated with oxidative damage caused by Cu exposure via regulating DAF-16/FoxO and SKN-1/Nrf2 pathways and intestinal flora to eliminate excess ROS. Our study provides a theoretical basis formulating future strategy of probiotics against heavy metal contamination.

Fish Oil Ameliorates Vibrio parahaemolyticus Infection in Mice by Restoring Colonic Microbiota, Metabolic Profiles, and Immune Homeostasis.

The effect of fish oil (FO) on colonic function, immunity, and microbiota was investigated in Vibrio parahaemolyticus (Vp)-infected C57BL/6J mice. Mice intragastrically presupplemented with FO (4.0 mg) significantly reduced Vp infection as evidenced by stabilizing body weight and reducing disease activity index score and immune organ ratios. FO minimized colonic pathological damage, strengthened the mucosal barrier, and sustained epithelial permeability by increasing epithelial crypt depth, goblet cell numbers, and tight junctions and inhibiting colonic collagen accumulation and fibrosis protein expression. Mechanistically, FO enhanced immunity by decreasing colonic CD3+ T cells, increasing CD4+ T cells, downregulating the TLR4 pathway, reducing interleukin-17 (IL-17) and tumor necrosis factor-α, and increasing immune cytokine IL-4 and interferon-γ levels. Additionally, FO maintained colonic microbiota eubiosis by improving microbial diversity and boosting Clostridium, Akkermansia, and Roseburia growth and their derived propionic acid and butyric acid levels. Collectively, FO alleviated Vp infection by enriching beneficial colonic microbiota and metabolites and restoring immune homeostasis.

Nutrients mediate caffeine inhibition of Escherichia coli.

The consumption of coffee and other caffeinated drinks is increasingly popular across the globe. In the United States, 90% of adults consume at least one caffeinated beverage a day. While caffeine consumption of up to 400 mg/d is not generally associated with negative effects on human health, the impact of caffeine on the gut microbiome and individual gut microbiota remains unclear. We examined the effect of caffeine on the growth rate of Escherichia coli, a bacterium commonly found in the human gut, when grown aerobically or anaerobically in nutrient-rich or minimal medium. A significant negative correlation was observed between caffeine concentration and growth rate under all conditions, suggesting that caffeine can act as an antimicrobial agent when ingested. Caffeine reduced growth rates significantly more in nutrient-poor, but not in anoxic, conditions. Given the highly variable nutrient and oxygen conditions of the gut, these results suggest a need to further explore caffeine's inhibitory effects on the gut microbiome and its relation to human health.

Oral Microalgae-Nano Integrated System against Radiation-Induced Injury.

The increasing applications of ionizing radiation in society raise the risk of radiation-induced intestinal and whole-body injury. Astaxanthin is a powerful antioxidant to reduce the reactive oxygen generated from radiation and the subsequent damage. However, the oral administration of astaxanthin remains challenging owing to its low solubility and poor bioavailability. Herein, we facilely construct an orally used microalgae-nano integrated system (SP@ASXnano) against radiation-induced intestinal and whole-body injury, combining natural microalgae Spirulina platensis (SP) with astaxanthin nanoparticles (ASXnano). SP and ASXnano show complementation in drug delivery to improve distribution in the intestine and blood. SP displays limited gastric drug loss, prolonged intestinal retention, constant ASXnano release, and progressive degradation. ASXnano improves drug solubility, gastric stability, cell uptake, and intestinal absorption. SP and ASXnano have synergy in many aspects such as anti-inflammation, microbiota protection, and fecal short-chain fatty acid up-regulation. In addition, the system is ensured with biosafety for long-term administration. The system organically combines the properties of microalgae and nanoparticles, which was expected to expand the medical application of SP as a versatile drug delivery platform.

Metagenome-mining indicates an association between bacteriocin presence and strain diversity in the infant gut.

BACKGROUND: Our knowledge about the ecological role of bacterial antimicrobial peptides (bacteriocins) in the human gut is limited, particularly in relation to their role in the diversification of the gut microbiota during early life. The aim of this paper was therefore to address associations between bacteriocins and bacterial diversity in the human gut microbiota. To investigate this, we did an extensive screening of 2564 healthy human gut metagenomes for the presence of predicted bacteriocin-encoding genes, comparing bacteriocin gene presence to strain diversity and age. RESULTS: We found that the abundance of bacteriocin genes was significantly higher in infant-like metagenomes (< 2 years) compared to adult-like metagenomes (2-107 years). By comparing infant-like metagenomes with and without a given bacteriocin, we found that bacteriocin presence was associated with increased strain diversities. CONCLUSIONS: Our findings indicate that bacteriocins may play a role in the strain diversification during the infant gut microbiota establishment.

Effects of SGLT2 inhibitors on the intestinal bacterial flora in Japanese patients with type 2 diabetes mellitus.

Selective inhibitors of sodium glucose co-transporter-2 (SGLT2) suppress renal glucose reabsorption and promote urinary glucose excretion, thereby lowering blood glucose. SGLT2 inhibitors have been reported to reduce body weight. However, the mechanism underlying the reduction in the body weight induced by SGLT2 inhibitor treatment remains to be elucidated. In this study, we investigated the effects of SGLT2 inhibitors on the intestinal bacterial flora. A total of 36 Japanese patients with type 2 diabetes mellitus received a SGLT2 inhibitor (luseogliflozin or dapagliflozin) for 3 months, and the prevalences of balance-regulating bacteria and balance-disturbing bacteria in the feces of the patients before and after SGLT2 inhibitor treatment were determined. SGLT2 inhibitor treatment was associated with a significant increase of the overall prevalence of the 12 types of balance-regulating bacteria. In addition, significant increases in the prevalences of the short-chain fatty acid (SCFAs)-producing bacteria among the balance-regulating bacteria were also observed. Individual analyses of the balance-regulating bacteria revealed that the SGLT2 inhibitor treatment was associated with a significant increase in the prevalence of Ruminococci, which are balance-regulating bacteria classified as SCFAs-producing bacteria. However, SGLT2 inhibitor had no effect on the balance-disturbing bacteria. These results suggested that SGLT2 inhibitor treatment was associated with an overall increase in the prevalence of balance-regulating bacteria. Among the balance-regulating bacteria, the prevalences of SCFAs-producing bacteria increased. SCFAs have been reported to prevent obesity. The results of the present study suggest that SGLT2 inhibitors might induce body weight reduction via their actions on the intestinal bacterial flora.

Study of anti-fatigue activity of polysaccharide from fruiting bodies of Armillaria gallica.

Fatigue is a common physiological response that is closely related to energy metabolism. Polysaccharides, as excellent dietary supplements, have been proven to have a variety of pharmacological activities. In this study, A 23.007 kDa polysaccharide from Armillaria gallica (AGP) was purified and performed structural characterization, including analysis of homogeneity, molecular weight and monosaccharide composition. Methylation analysis is used to analyze the glycosidic bond composition of AGP. The mouse model of acute fatigue was used to evaluate the anti-fatigue effect of AGP. AGP-treatment improved exercise endurance in mice and reduced fatigue symptoms caused by acute exercise. AGP regulated the levels of adenosine triphosphate, lactic acid, blood urea nitrogen and lactate dehydrogenase, muscle glycogen and liver glycogen of acute fatigue mice. AGP affected the composition of intestinal microbiota, the changes of some intestinal microorganisms are correlated with fatigue and oxidative stress indicators. Meanwhile, AGP reduced oxidative stress levels, increased antioxidant enzyme activity and regulated the AMP-dependent protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathway. AGP exerted an anti-fatigue effect through modulation of oxidative stress, which is related to intestinal microbiota.

Adverse effects of titanium dioxide nanoparticles on beneficial gut bacteria and host health based on untargeted metabolomics analysis.

Titanium dioxide (TiO2) is a common additive in foods, medicines, and personal care products. In recent years, nano-scale particles in TiO2 additives have been an increasing concern due to their potential adverse effects on human health, especially gut health. The objective of this study was to determine the impact of titanium dioxide nanoparticles (TiO2 NPs, 30 nm) on beneficial gut bacteria and host response from a metabolomics perspective. In the in vitro study, four bacterial strains, including Lactobacillus reuteri, Lactobacillus gasseri, Bifidobacterium animalis, and Bifidobacterium longum were subjected to the treatment of TiO2 NPs. The growth kinetics, cell viability, cell membrane permeability, and metabolomics response were determined. TiO2 NPs at the concentration of 200 µg/mL showed inhibitory effects on the growth of all four strains. The confocal microscope results indicated that the growth inhibitory effects could be associated with cell membrane damage caused by TiO2 NPs to the bacterial strains. Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health. In the in vivo study, mice were fed with TiO2 NPs (0.1 wt% in diet) for 8 weeks. Mouse urine was collected for metabolomics analysis and the tryptophan metabolism pathway was also significantly affected in TiO2 NPs-fed mice. Moreover, four neuroprotective metabolites were significantly reduced in both in vitro bacteria and in vivo urine samples. Overall, this study provides insights into the potential adverse effects of TiO2 NPs on gut bacteria and the metabolic responses of both bacteria and host. Further research is needed to understand the causality between gut bacteria composition and the metabolism pathway, which is critical to monitor the gut-microbiome mediated metabolome changes in toxicological assessment of food components.

A Novel E3 Probiotics Formula Restored Gut Dysbiosis and Remodelled Gut Microbial Network and Microbiome Dysbiosis Index (MDI) in Southern Chinese Adult Psoriasis Patients.

Psoriasis is a common chronic immune-mediated inflammatory skin disease with the association of various comorbidities. Despite the introduction of highly effective biologic therapies over the past few decades, the exact trigger for an immune reaction in psoriasis is unclear. With the majority of immune cells residing in the gut, the effect of gut microbiome dysbiosis goes beyond the gastrointestinal site and may exacerbate inflammation and regulate the immune system elsewhere, including but not limited to the skin via the gut-skin axis. In order to delineate the role of the gut microbiome in Southern Chinese psoriasis patients, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profile of 58 psoriasis patients against 49 healthy local subjects presumably with similar lifestyles. Blautia wexlerae and Parabacteroides distasonis were found to be enriched in psoriasis patients and in some of the healthy subjects, respectively. Metabolic functional pathways were predicted to be differentially abundant, with a clear shift toward SCFA synthesis in healthy subjects. The alteration of the co-occurrence network was also evident in the psoriasis group. In addition, we also profiled the gut microbiome in 52 of the 58 recruited psoriasis patients after taking 8 weeks of an orally administrated novel E3 probiotics formula (with prebiotics, probiotics and postbiotics). The Dermatological Life Quality Index (p = 0.009) and Psoriasis Area and Severity Index (p < 0.001) were significantly improved after taking 8 weeks of probiotics with no adverse effect observed. We showed that probiotics could at least partly restore gut dysbiosis via the modulation of the gut microbiome. Here, we also report the potential application of a machine learning-derived gut dysbiosis index based on a quantitative PCR panel (AUC = 0.88) to monitor gut dysbiosis in psoriasis patients. To sum up, our study suggests the gut microbial landscape differed in psoriasis patients at the genera, species, functional and network levels. Additionally, the dysbiosis index could be a cost-effective and rapid tool to monitor probiotics use in psoriasis patients.

Multi-omics approach to study the dual effects of novel proteins on the intestinal health of juvenile largemouth bass (Micropterus salmoides) under an alternate feeding strategy.

Introduction: In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant. Methods: Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days. Results: The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1ß/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson's correlation. Discussion: Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.

Lithium and Microorganisms: Biological Effects and Mechanisms.

This review covers the lithium effects on microorganisms, including gut and soil bacteria. Available studies of the biological effects of lithium salts have revealed a wide range of different effects of lithium cations on various microorganisms, but so far, the study of this direction has not been summarized enough. Here we consider the confirmed and various plausible mechanisms of lithium action on microorganisms. Special emphasis is placed on assessing the effect of lithium ions under oxidative stress and adverse environmental conditions. The impact of lithium on the human microbiome is also being reviewed and discussed. Controversial effects of lithium have been shown, including the inhibitory and stimulating effects of lithium on bacterial growth.

Field-realistic dose of cefotaxime enhances potential mobility of ß-lactam resistance genes in the gut microbiota of zebrafish (Danio rerio).

With large amounts of cephalosporin end up in natural ecosystems, water has been acknowledged as the large reservoir of ß-lactam resistance over the past decades. However, there is still insufficient knowledge available on the function of the living organisms to the transmission of antibiotic resistance. For this reason, in this study, using adult zebrafish (Danio rerio) as animal model, exposing them to environmentally relevant dose of cefotaxime for 150 days, we asked whether cefotaxime contamination accelerated ß-lactam resistance in gut microbiota as well as its potential transmission. Results showed that some of ß-lactam resistance genes (ßRGs) were intrinsic embedded in intestinal microbiome of zebrafish even without antibiotic stressor. Across cefotaxime treatment, the abundance of most ßRGs in fish gut microbiome decreased apparently in the short term firstly, and then increased with the prolonged exposure, forming distinctly divergent ßRG profiles with antibiotic-untreated zebrafish. Meanwhile, with the rising concentration of cefotaxime, the range of ßRGs' host-taxa expanded and the co-occurrence relationships of mobile genetics elements (MGEs) with ßRGs intensified, indicating the enhancement of ßRGs' mobility in gut microbiome when the fish suffered from cefotaxime contamination. Furthermore, the path of partial least squares path modeling (PLS-PM) gave an integral assessment on the specific causality of cefotaxime treatment to ßRG profiles, showing that cefotaxime-mediated ßRGs variation was most ascribed to the alteration of MGEs under cefotaxime stress, followed by bacterial community, functioning both direct influence as ßRG-hosts and indirect effects via affecting MGEs. Finally, pathogenic bacteria Aeromonas was identified as the critical host for multiple ßRGs in fish guts, and its ß-lactam resistance increased over the duration time of cefotaxime exposure, suggesting the potential spreading risks for the antibiotic-resistant pathogens from environmental ecosystems to clinic. Overall, our finding emphasized cefotaxime contamination in aquatic surroundings could enhance the ß-lactam resistance and its transmission mobility in fish bodies.