Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway.

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

Impact of buffered sodium butyrate as a partial or total dietary alternative to lincomycin on performance, IGF-1 and TLR4 genes expression, serum indices, intestinal histomorphometry, Clostridia, and litter hygiene of broiler chickens.

BACKGROUND: Sodium butyrate (SB) is a short-chain fatty acid and a safe antibiotic alternative. During 35 days, this study compared the impact of coated SB (Butirex C4) and lincomycin (Lincomix) on broiler growth, gut health, and litter hygiene in 1200 one-day-old Ross-308 broiler chicks that were randomly assigned into 5-dietary groups with 5-replications each. Groups divided as follows: T1: Basal diet (control), T2: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds), T3: Basal diet with 100 g/ton lincomycin, T4: Basal diet with buffered SB (0.5 kg/ton starter feed, 0.25 kg/ton grower-finisher feeds) + 50 g/ton lincomycin, and T5: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds) + 50 g/ton lincomycin. Birds were housed in a semi-closed deep litter house, where feed and water were available ad libitum. Results were statistically analyzed using ANOVA and Tukey's post hoc tests. RESULTS: Combined dietary supplementation with SB and lincomycin (T4 and T5) significantly enhanced body weights, weight gains, feed conversion ratio, and profitability index. Also, carcasses in T4 and T5 exhibited the highest dressing, breast, thigh, and liver yields. T5 revealed the best blood biochemical indices, while T3 showed significantly elevated liver and kidney function indices. T4 and T5 exhibited the highest expression levels of IGF-1 and TLR4 genes, the greatest villi length of the intestinal mucosa, and the lowest levels of litter moisture and nitrogen. Clostridia perfringens type A alpha-toxin gene was confirmed in birds' caeca, with the lowest clostridial counts defined in T4. CONCLUSIONS: Replacing half the dose of lincomycin (50 g/ton) with 0.5 or 1 kg/ton coated SB as a dietary supplement mixture showed the most efficient privileges concerning birds' performance and health.

Panax quinquefolius Polysaccharides Ameliorate Antibiotic-Associated Diarrhoea Induced by Lincomycin Hydrochloride in Rats via the MAPK Signaling Pathways.

American ginseng (Panax quinquefolius L.) is an herbal medicine with polysaccharides as its important active ingredient. The purpose of this research was to identify the effects of the polysaccharides of P. quinquefolius (WQP) on rats with antibiotic-associated diarrhoea (AAD) induced by lincomycin hydrochloride. WQP was primarily composed of galacturonic acid, glucose, galactose, and arabinose. The yield, total sugar content, uronic acid content, and protein content were 6.71%, 85.2%, 31.9%, and 2.1%, respectively. WQP reduced the infiltration of inflammatory cells into the ileum and colon, reduced the IL-1ß, IL-6, IL-17A, and TNF-α levels, increased the levels of IL-4 and IL-10 in colon tissues, improved the production of acetate and propionate, regulated the gut microbiota diversity and composition, improved the relative richness of Lactobacillus and Bacteroides, and reduced the relative richness of Blautia and Coprococcus. The results indicated that WQP can enhance the recovery of the intestinal structure in rats, reduce inflammatory cytokine levels, improve short-chain fatty acid (SCFA) levels, promote recovery of the gut microbiota and intestinal mucosal barrier, and alleviate antibiotic-related side effects such as diarrhoea and microbiota dysbiosis caused by lincomycin hydrochloride. We found that WQP can protect the intestinal barrier by increasing Occludin and Claudin-1 expression. In addition, WQP inhibited the MAPK inflammatory signaling pathway to improve the inflammatory status. This study provides a foundation for the treatment of natural polysaccharides to reduce antibiotic-related side effects.

Effects of broad-spectrum antibiotics on the metabolism and pharmacokinetics of ginsenoside Rb1: a study on rats׳ gut microflora influenced by lincomycin.

Ginsenoside Rb1 is a biologically active compound that is abundant in ginseng (Panax ginseng). It has been reported that ginsenosides could be metabolized by enzymes and bacteria in the large intestine. In this study, the effects of intestinal bacteria on the metabolism and pharmacokinetics of ginsenoside Rb1 were investigated using lincomycin-treated rat models (4.8g/kg and 0.12g/kg). Specifically, ginsenoside Rb1 was incubated anaerobically with rat fecal suspensions obtained from the control and two model groups at 0, 6, 12, 24, and 48h. Ginsenoside Rb1 and its metabolites were determined by HPLC analysis. Compared with the normal rats case where Rd and compound K were detected in the incubation mixture, ginsenoside Rd and F2 were found in the 0.12g/kg group, but only Rd was found in the 4.8g/kg group. Moreover, fecal ß-glucosidase activity was significantly lower in lincomycin-treated (0.12g/kg and 4.8g/kg) model rats. After administration of Rb1 to rats, ginsenoside Rb1 and its metabolites Rd, Rg3, and Rh2 were detectable in normal rat urine, whereas none was detected in the two model groups. The plasma concentration-time Rb1 were compared between model groups and normal rats. The systemic exposure as evidenced by the AUC and T1/2 values was significantly higher in model groups than in normal rats. Our findings demonstrated that consumption of lincomycin could lead to the formation of specific metabolites and pharmacokinetic changes of ginsenoside Rb1 in the gut, attributed to alterations in metabolic activities of intestinal bacteria. Our results also suggested that patients who want to use intestinal bacteria-metabolized drugs such as ginseng (Panax ginseng) should pay attention to the profile of intestinal bacteria or potential drug interactions to ensure therapeutic efficacy.

Effect of extender supplementation with various antimicrobial agents on viability of Brucella ovis and Actinobacillus seminis in cryopreserved ovine semen.

The objective was to determine the effectiveness of various antimicrobial agents added to semen extender for inactivation of B. ovis or A. seminis in ovine semen after cryopreservation. In Experiment 1, 20 ejaculates from a crossbred ram infected with B. ovis were cryopreserved in Tris-based extenders with various antimicrobial agents: (I) control without antibiotics, (II) with penicillin and streptomycin (1000 IU/mL and 1 mg/mL, respectively), (III) lincomycin (0.15 mg/mL), (IV) sulphadiazine (0.60 mg/mL), and (V) gentamicin sulphate (0.25 mg/mL). Semen was stored in 0.25 mL straws at a final concentration of 150 × 10(6) spermatozoa/mL. After thawing (37 °C for 30 s), sperm total motility (TM), sperm morphology, integrity of sperm membranes, and bacterial growth were assessed. In Experiment 2, six B. ovis isolates were separately inoculated into aliquots of a fresh ejaculate from a B. ovis-free ram. Mock inoculated semen was processed for cryopreservation using the five extenders described above, and bacteriologically evaluated after thawing. In Experiment 3, sensitivity of A. seminis to the same antimicrobial agents was evaluated by inoculating an ejaculate from an A. seminis and B. ovis-free ram. There were no significant differences among treatments in post-thawing sperm parameters. B. ovis was isolated from 100% (20/20), 0% (0/20), 95% (19/20), 100% (20/20), and 5% (1/20) of semen samples diluted in tris-based extender of untreated (I) and treated semen samples with antimicrobial agents II, III, IV, and V, respectively. Frequencies of isolation from samples treated with antimicrobial agent II and V were significantly lower than untreated ones (P < 0.05). There were no significant differences in the profile of antimicrobial resistance of different B. ovis isolates. A. seminis had a similar sensitivity to the antimicrobial agents. We concluded that addition of a combination of penicillin and streptomycin or gentamicin alone to ram semen cryo-extenders inactivated B. ovis and A. seminis.

Influence of antibiotic therapy on serum levels of reactive oxygen species in ovariectomized bitches.

This study was conducted on 60 ovariectomized bitches. The objectives were to measure the mean reactive oxygen species (ROS) concentrations before, during and after surgery, and to investigate the effect of the administration of five different antibiotic treatments: amoxicillin, benzylpenicillin/dihydrostreptomycin, sulfametazine/sulfamerazine/sulfathiazole, enrofloxacin, lincomycin/spectinomycin. The first value recorded represented the mean ROS concentration in anestral bitches and constitutes a reference level with which to compare the subsequent measurements. After premedication, induction of anesthesia and during maintenance and surgery, ROS serum concentrations showed constant values until the end of surgery. After surgery and during antibiotic administration, an increase in ROS concentration occurred, which differed among the five groups in relation to the antibiotics employed. The lowest increases occurred in the groups treated with the combination of lincomycin/spectinomycin, and with amoxicillin; whereas the highest increases were detected in the group treated with enrofloxacin. The three other antibiotics showed an intermediate level of influence on oxidative status.

Biofilm formation of the pathogens of fatal bacterial granuloma after trauma: potential mechanism underlying the failure of traditional antibiotic treatments.

The pathogen of a new type of disease - fatal bacterial granuloma after trauma (FBGT) - was found to be Propionibacterium acnes (P. acnes). Although in vitro studies showed that the pathogenic P. acnes are sensitive to conventional antibiotics, treatments of FBGT patients with these antibiotics were ineffective. The underlying mechanisms were not clear. Since P. acnes are able to form biofilm on orthopaedic biomaterials in vitro, and pathogenic P. acnes of acnes vulgaris was known to form biofilm in vivo, we hypothesize that the pathogens of FBGT are also able to form biofilm during the pathogenesis, which may be 1 of the reasons for antibiotics tolerance of FBGT. Biofilm forming capacity of the pathogens of FBGT were examined with XTT reduction method, as well as with scanning electron microscope. The effect of long-term subminimal inhibitory concentration (MIC) lincomycin on the biofilm forming ability of the pathogens was also tested. Our results show that both the type strain (NCTC737) and the pathogenic P. acnes of FBGT can form biofilm in vitro. These data demonstrated the biofilm formation of the FBGT pathogens in vitro, and its acceleration by lincomycin, which may be 1 of the major mechanisms for the failure of antibiotic treatment.

Effects of griseoviridin and viridogrisein against swine dysentery in experimental infection by using mice and pigs.

Griseoviridin, a known antibiotic produced by Streptomyces cacaoi subsp. cacaoi, was found to be active against Brachyspira hyodysenteriae--the bacterium causing swine dysentery. An in vitro synergism is observed when it is used in combination with viridogrisein--a simultaneously produced antibiotic. In mouse experiments, the effect of griseoviridin alone was less than that of lincomycin--a commercially available swine dysentery medication. However, a 1:1 mixture of griseoviridin and viridogrisein revealed a noticeable synergistic effect. In an evaluation using pigs artificially infected with B. hyodysenteriae, a large difference was not observed between the effect of griseoviridin alone and that in combination with viridogrisein. Nevertheless, griseoviridin alone exhibited a therapeutic effect superior to that of lincomycin.

Broiler performance and intestinal alterations when fed drug-free diets.

A study was carried out to investigate the effects of a drug-free feeding program on broiler performance and intestinal morphology. Chicks vaccinated against coccidia were randomly assigned to 4 dietary treatments: 1) negative control (NC), basal diet; 2) positive control (PC), diet 1 + Lincomycin; 3) program 1 (PG1); diet 1 + Bio-Mos, Vegpro, MTB-100, Acid Pak 4-Way, and All-Lac XCL; 4) and program 2 (PG2), diet 1 + Bio-Mos and All-Lac XCL, each of which were assigned to 13 pens (48 birds in each of 52 pens). Growth traits (BW, feed intake, yield, mortality, BW gain, and feed conversion rate) were obtained through 49 d. At d 14, 3 chicks per pen were challenged with coccidia. Segments of duodenum, ileum, and ceca were removed to measure intestinal morphology at d 14, 28, 35, and 49. Final BW gain of broilers on PC (2.736 kg) was numerically higher than those for NC (2.650 kg). Cumulative feed conversion rate at d 49 was improved (P < 0.05) in birds consuming PC and PG2 compared with NC. Overall, mortality was higher for birds consuming the NC (P < 0.05) than the PC, PG1, and PG2 diets. Interaction of dietary treatments with age and age alone were evident (P < 0.0001) for morphology of duodenum, ileum, and ceca. Lamina propria in ceca was thicker (P < 0.008) in broilers consuming the NC than PG1 and PG2 diets. The results of this study indicated that feeding birds without growth promoters resulted in higher mortality and decreased growth performance than did feeding a diet with an antibiotic, and the combination of Bio-Mos and All-Lac XCL helped to reduce negative effects.

Photoinactivation of photosystem II complexes and photoprotection by non-functional neighbours in Capsicum annuum L. leaves.

Leaf segments from Capsicum annuum plants grown at 100 micromol photons m(-2) s(-1) (low light) or 500 micromol photons m(-2) s(-1) (high light) were illuminated at three irradiances and three temperatures for several hours. At various times, the remaining fraction (f) of functional photosystem II (PS II) complexes was measured by a chlorophyll fluorescence parameter (1/Fo -1/Fm, where Fo and Fm are the fluorescence yields corresponding to open and closed PS II traps, respectively), which was in turn calibrated by the oxygen yield per saturating single-turnover flash. During illumination of leaf segments in the presence of lincomycin, an inhibitor of chloroplast-encoded protein synthesis, the decline of f from 1.0 to about 0.3 was mono-exponential. Thereafter, f declined much more slowly, the remaining fraction (approximately equals 0.2) being able to survive prolonged illumination. The results can be interpreted as being in support of the hypothesis that photoinactivated PS II complexes photoprotect functional neighbours (G. Oquist et al. 1992, Planta 186: 450-460), provided it is assumed that a photoinactivated PS II is initially only a weak quencher of excitation energy, but becomes a much stronger quencher during prolonged illumination when a substantial fraction of PS II complexes has also been photoinactivated. In the absence of lincomycin, photoinactivation and repair of PS II occur in parallel, allowing f to reach a steady-state value that is determined by the treatment irradiance, temperature and growth irradiance. The results obtained in the presence and absence of lincomycin are analysed according to a simple kinetic model which formally incorporates a conversion from weak to strong quenchers, yielding the rate coefficients of photoinactivation and of repair for various conditions, as well as gaining an insight into the influence off on the rate coefficient of photoinactivation. They demonstrate that the method is a convenient alternative to the use of radiolabelled amino acids for quantifying photoinactivation and repair of PS II in leaves.

A differential response in turkey poults to various antibiotics in diets designed to be deficient or adequate in certain essential nutrients.

Two experiments, each consisting of two trials, were conducted with day-old Nicholas Large White turkey poults to compare the effectiveness of four antibiotics for growth promotion and the utilization of sulfur amino acids. A corn-soybean meal basal diet that contained no supplemental methionine, choline, or inorganic sulfate was used in order to furnish nutritional stress. The diet was calculated to contain 25.4% protein, .448% methionine, .403% cystine, 1014 mg/kg choline, and 2990 kcal metabolizable energy/kg. In Experiment 1, a 2 X 4 factorial arrangement of treatments was used. This included two levels, (0% (control) and .18%), of supplemental DL-methionine and no antibiotic or bacitracin MD, flavomycin, or virginiamycin; antibiotics were fed at 50, 2, and 20 g/ton, respectively. In Experiment 2, lincomycin also was included as a treatment (at 4 g per ton) resulting in a 2 X 5 factorial arrangement of treatments. Only the addition of Virginiamycin to the control diet in Experiment 1 resulted in significantly increased body weights. Supplementation by .18% methionine increased body weights and feed efficiency. In addition, all three antibiotics increased body weights significantly when added to the .18% methionine diets. Feed efficiency values were improved by all four antibiotics at both methionine levels. In Experiment 2, increases in body weights similar to those in Experiment 1 were obtained with the addition of .18% methionine to the basal diets. Addition of lincomycin and virginiamycin improved body weights and feed efficiencies in the presence and absence of supplemental methionine.

The susceptibility of a strain of Leptospira interrogans serogroup icterohaemorrhagiae to amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline.

The failure of prophylactic penicillin to prevent a laboratory acquired case of Icterohaemorrhagiae leptospirosis prompted determination of the MIC and MBC of amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline for the infecting strain. Amoxycillin followed by erythromycin were the most effective, with MBCs of 0.5 mg/l after 7 days exposure and 0.1 mg/l after 21 days exposure respectively. Leptospires grew in the presence of high concentrations of tetracycline hydrochloride and oxytetracycline after prolonged incubation. This effect was less pronounced with minocycline, with MIC's of 0.025, 0.05 and 0.1 mg/l after 7, 14 and 21 days exposure respectively. The MIC of lincomycin was 0.25 mg/l at each time interval. These results support the high dose, long duration antibiotic regimens recommended in the literature.

New trends in the chemotherapy of staphylococcal infections.

The authors evaluated the susceptibility of some antibiotics against several Staphylococci subdivided in lyogroups and different resistance patterns: methicillin-susceptible/penicillin-susceptible (MS/PS), methicillin-susceptible/penicillin-resistant (MS/PR), methicillin-resistant/penicillin-resistant (MR/PR) and methicillin-resistant/penicillin-susceptible (MR/PS). The antimicrobial agents used were: methicillin, penicillin, rifampin, tetracycline, lincomycin, erythromycin, gentamicin and netilmicin. Netilmicin showed better activity against all Staphylococcus strains tested, particularly against coagulase-negative.

Antibiotic treatment of cervicofacial actinomycosis for patients allergic to penicillin: a clinical and in vitro study.

The minimum inhibitory concentrations for erythromycin, clindamycin, lincomycin, tetracycline and minocycline have been determined for 92 clinical and three culture collection isolates of Actinomyces. From a consideration of MIC values and expected serum levels from oral therapy, minocycline was the drug of choice for the treatment of actinomycosis in patients allergic to penicillin. The serum levels of six patients allergic to penicillin, treated with oral minocycline 1 g/day were monitored and found to exceed the MIC for the Actinomyces species responsible for the condition. In all six Actinomycosis cases resolution was achieved in 8-16 weeks of oral minocycline therapy with no recrudescence for 1 year.

[Tolerance of group A streptococci to the bactericidal effect of various antibiotics]. / Izuchenie tolerantnosti streptokokkov gruppy A k bakteritsidnomu deistviiu nekotorykh antibiotikov.

The MICs and MBCs (minimum bactericidal concentration) of 6 antibiotics (benzylpenicillin, oxacillin, cephalothin, ristomycin, erythromycin and lincomycin) for 50 strains of group A streptococci were determined with serial dilutions in a liquid medium (the medium for isolation of streptococci of the I. I. Mechnikov Moscow Research Institute of Vaccines and Sera) followed by volumetric platings on a solid medium (the same medium supplemented with 1.5 per cent agar). The results are discussed in relation to the problem of Streptococci tolerance to the bactericidal effect of the antibiotics.

Possible role of lincomycin-therapy in the genetic alteration of a staphylococcus epidemic population.

In a staphylococcosis epidemic occurring in a child community, the proportion of inducible lincomycin resistance has risen significantly in the bacterium population. This conveyed the possibility that lincomycin or its derivatives may induce a lincomycin resistance in Staphylococcus aureus as it is already known in streptococci. Examination of human and animal samples obtained during lincomycin treatment showed that lincomycin had no role in the induction of resistance; the agent can effectively be applied against pathogens of the above-mentioned phenotype. Immunological examination of serum samples provided opportunity for a more exact localization of the protein-linkage of lincomycin.

Effects of cloxacillin, doxycycline, fusidic acid and lincomycin on mineralization and solubility of collagen in young rats.

The antibiotics doxycycline, fusidic acid and lincoymcin have recently been shown to reduce growth of bones and tensile strength of skin in young rats. Such adverse effects were not found in rats receiving cloxacillin. The present investigation deals with the influences of these four antibiotics on the mineralization of bones and on the solubility of collagen in skin. In rats receiving doxycycline the content of calcium and phosphorus in bones and the concentration of albumin in serum were reduced. None of the antibiotics had a detectable effect on the solubility of collagen.

The effect of adsorbant and anti-inflammatory drugs on secretion in ligated segments of pig intestine infected with Escherichia coli.

Four adsorbant drug preparations, Kaopectate, colloidal Attapulgite, noncolloidal Attapulgite and Pepto-bismol were investigated for their effects on fluid accumulation in ligated segments of pig intestine inoculated with enteropathogenic Escherichia coli. Two anti-inflammatory drugs. aspirin and methylprednisolone, and two antibiotics, lincomycin and polymyxin B, were also tested. All the drugs except the two anti-inflammatory products were given by injection into the lumen of the intestine. Aspirin was given orally and methylprednisolone was given intramuscularly. The antibiotics were tested at levels at which they had no significant antibacterial effect in in vitro tests. The adsorbant drugs colloidal Attapulgite and Pepto-bismol were shown to be effective in reducing fluid accumulation in ligated segments of pig intestine infected with enteropathogenic E. coli. In the case of Peptobismol this effect was associated with an antibacterial effect as well as an antitoxic effect, probably due to its adsorbant properties. It is possible that an aspirin-like effect in the gut due to the active ingredient bismuth subsalicylate may have contributed to the effectiveness of Pepto-bismol. Colloidal Attapulgite was demonstrated to have an antitoxic effect but did not have an antibacterial effect. In high doses, the anti-inflammatory drugs acetylsalicylic acid and methylprednisolone were marginally effective in reduction of fluid accumulation in the same test system. Lincomycin was shown to reduce intestinal fluid secretion, whereas polymyxin B had no effect.