Abx Group Research Articles

Impact of Antibacterials on the Quality of Anticoagulation Control in Patients Initiating Warfarin Therapy.

Warfarin interacts with antibacterials to prolong the prothrombin time international normalized ratio (PT-INR) and increase the risk of bleeding. Patients initiating warfarin therapy often undergo precise dosage adjustments; however, the clinical implications of these interactions with antibacterials remain unclear. This study aimed to clarify the effect of antibacterials on PT-INR during the warfarin induction phase. This was a retrospective, observational study. Patients who were newly treated with warfarin after cardiovascular surgery were included. The primary endpoint was the comparison of the maximum PT-INR and time in therapeutic range (TTR) after warfarin initiation between the antibacterial-treated (ABx) and non-treated (non-ABx) groups. The maximum PT-INR was significantly higher in the ABx group (which included β-lactams, glycopeptides, quinolones, tetracyclines, and aminoglycosides) than in the non-ABx group (median [interquartile range] 2.37 [2.03-2.71] vs. 2.08 [1.93-2.33]; P = 0.005); however, the TTR did not differ significantly (65% [44-76] vs. 71% [43-85]; P = 0.150). The odds ratio for maximum PT-INR >2.6 with antimicrobial therapy was 2.51 (95% confidence interval 1.21-5.21). Antibacterial therapy was a risk factor for a maximum PT-INR >2.6. However, there was no association with the TTR, which is a marker of good outcomes. This was due to the strict warfarin dosing regimen according to the algorithm, which immediately and appropriately adjusted for PT-INR overexpansion. Antibacterials have been suggested to increase PT-INR during the induction phase of warfarin. However, with strict dose adjustments, the clinical impact on the PT-INR and TTR is likely limited.

Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.

Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice. Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP. Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%). FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.

Are prophylactic antibiotics effective in preventing osteoradionecrosis after high-risk dental extractions?

A systematic review and meta-analysis. To assess and compare the effectiveness of different adjunctive treatments during tooth extraction in post-radiotherapy head and neck patients for preventing osteoradionecrosis (ORN). Two independent reviewers conducted an electronic search through PubMed, Embase, Cochrane Libraries, Scopus and Web of Science databases using relevant search terms. Additionally, references of relevant articles were manually searched for eligible studies. Included were full-length articles (randomized controlled trials (RCTs), clinical trials, or observational studies) published in English, reporting on ORN occurrence after dental extraction, with or without adjunctive interventions, in patients who had previous radiotherapy. Data extraction was similarly performed by two independent researchers. For quality assessment, bias in observational studies was evaluated using the ROBINS-I tool, while the RoB 2 tool was used for RCTs. One-arm meta-analyses estimated pooled ORN prevalence rates for different adjunctive treatments based on patient-level outcomes. For studies with direct comparisons between two modalities, pooled odds ratios for ORN were calculated using pairwise meta-analyses. This systematic review followed PRISMA guidelines and was registered in the PROSPERO database. A total of 29 studies with 1520 patients were included, comprising 4 RCTs, 4 prospective studies, and 21 retrospective observational studies. Five adjunctive treatment modalities around the time of dental extractions were identified: hyperbaric oxygen (HBO), pentoxifylline-tocopherol (PENTO), antibiotics (ABX), platelet-rich fibrin and photobiomodulation. Of the 25 observational studies included, 11 had a serious risk of bias, while all RCTs but 1 had low risk of bias. Egger's test showed no publication bias for the HBO and ABX groups (p > 0.05). Antibiotics were used in 17 studies, with significant variations in preoperative and postoperative protocols. Most studies utilized penicillin or clindamycin. The pooled prevalence of ORN was significantly lower in the HBO (4.6%), PENTO (3.4%), and ABX (3.8%) groups compared to the Control (17.6%), as indicated by the non-overlapping 95% CIs between the Control and any of the intervention groups. In studies with direct comparisons, HBO exhibited lower odds of developing ORN than the Control (odds ratio [OR] = 0.27) and ABX (OR = 0.57), although these differences were not statistically significant. HBO, PENTO, and ABX show similar reduction in ORN rates compared to no intervention. Given its cost-effectiveness and accessibility, ABX may be the most practical prophylactic modality at present.

SP5.3 - Systematic review and meta-analysis of the management of acute uncomplicated diverticulitis: Time to change the traditional practice

Abstract Background To evaluate comparative outcomes of outpatient versus inpatient treatment and antibiotics versus no antibiotics approach in the treatment of uncomplicated (Hinchey 1a) acute diverticulitis. The protocol of this review was registered in PROSPERO (CRD42023488826). Methods A systematic online search was conducted using electronic databases. Comparative studies of outpatient (OP) versus inpatient (IP) treatment and antibiotics (ABX) versus no antibiotics (NABX) approach in the treatment of uncomplicated (Hinchey 1a) acute diverticulitis were included. The primary outcome was diverticulitis recurrence. Emergency surgical resection, elective surgical resection, development of complicated diverticulitis, mortality rate, and length of hospital (LOS) were the other evaluated secondary outcomes. Results The literature search identified 14 studies (n=3,875) comparing NABX (n=2,008) versus ABX (n=1,867). The NABX group showed a lower disease recurrence rate and shorter LOS compared with the ABX group (P=0.01) and (P=0.004). No significant difference was observed in emergency resections (P=0.33), elective resections (P=0.73), development of complicated diverticulitis (P=0.65), hospital re-admissions (P=0.65) and 30-day mortality rate (P=0.91). Twelve studies (n=2,286) compared OP (n=1,021) versus IP (n=1,265) management of uncomplicated acute diverticulitis. The two groups were comparable for the following outcomes: treatment failure (P=0.10), emergency surgical resection (P=0.40), elective resection (P=0.30), diverticulitis recurrence (P=0.22), and mortality (P=0.61). Conclusion Compared with the use of ABX, the NABX approach seems to provide similar clinical outcomes and shorter LOS. Moreover, OP treatment of Hinchey 1a acute diverticulitis is comparable with IP management and presumably leads to cost savings in depleted healthcare systems

Okra extract alleviates lipopolysaccharide-induced inflammation response through the regulation of bile acids, the receptor-mediated pathway, and gut microbiota.

Okra contains flavonoids and vitamin C as antioxidants and it contains polysaccharides as immunomodulators. Flavonoids regulate the inflammatory response in mice and may be related to gut microbiota. This study therefore aimed to investigate the impact of okra extract (OE) on inflammation in mice and to elucidate its underlying mechanism. Forty male Kunming (KM) mice were categorized into four groups: the control (CON) group, the lipopolysaccharide stimulation (LPS) group, the 5 mg mL-1 OE intervention (LPS + OE) group, and the 5 mg mL-1 OE supplementation plus mixed antibiotics (LPS + OE + ABX) group. The results showed that, compared with the OE group, the expression of inflammatory signaling pathway genes was upregulated and gut barrier genes were inhibited in the OE + ABX group. The Fxr receptor was activated and the abundance of Akkermansia was increased after OE supplementation, whereas the effect was reversed in the OE + ABX group. Meanwhile, Fxr was correlated positively with Akkermansia. The OE supplementation alleviated the inflammatory response in mice under LPS stimulation, accompanied by changes in gut microbiota and bile acid receptors, whereas the addition of antibiotics caused a disturbance to the gut microbiota in the OE group, thus reducing the effect of OE in alleviating the inflammatory response. © 2024 Society of Chemical Industry.

Macleaya cordata extract exhibits some potential as a surrogate antibiotic by improving gastrointestinal epithelial status and humoral response in goats

Macleaya cordata extract (MCE) is a potential replacement for antibiotics. In the current study, effects of MCE on the gastrointestinal health and humoral responses of host animals were explored. A total of 30 weanling goats with similar body weight of 9.15 ± 1.36 kg were randomly allocated into three groups (n = 10 per group): control group (CON group, fed with a basal diet), antibiotic group (Abx group, fed with the basal diet supplemented with 0.18 g/d vancomycin and 0.36 g/d neomycin), and MCE group (fed with the basal diet supplemented with 5 g/d MCE), for three weeks. Results showed that antibiotic addition decreased the height and area of rumen papillae, ruminal mucosa Toll-like receptor 8 (TLR8), interleukin-8 (IL-8) and interleukin-1β (IL-1β) gene relative expression levels and microbial diversity, altered the volatile fatty acid (VFA) profile in the rumen, and increased monocytes amount and CD4+ T cells percentage in the peripheral blood (P < 0.05) compared to CON group. MCE addition increased the average daily gain, ileal villus height, villus height/crypt depth, and immunoglobulin M (IgM) content in the peripheral blood (P < 0.05) compared to the CON. Additionally, MCE addition decreased the proportion of isobutyric acid in the chyme of the ileum (P = 0.005) compared to the CON group. These results suggest that antibiotic supplementation may suppress the epithelial state and microbial diversity and fermentation in goats, but stimulate cellular response to maintain the growth performance of goats. MCE administration improved the epithelial state and humoral response to promote the growth performance in goats.

Extended-duration antibiotics are not associated with a reduction in surgical site infection in patients with ovarian cancer undergoing cytoreductive surgery with large bowel resection

Objective(s)To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. MethodsA retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. ResultsIn total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). Conclusion(s)In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.

Efficacy and safety of chemoimmunotherapy in advanced non-small cell lung cancer patients with antibiotics-induced dysbiosis: a propensity-matched real-world analysis

PurposeThe gut microbiota is hypothesized as a prognostic biomarker for cancer immunotherapy. Antibiotic-induced dysbiosis negatively affects the clinical outcomes of immunotherapy. However, the effect of dysbiosis on the efficacy and safety of Chemoimmunotherapy (chemo-IOs), the frontline standard of care, in advanced non-small cell lung cancer (NSCLC) remains unknown. We aimed to compare the efficacy and safety of chemo-IOs in patients exposed to antibiotics before treatment with those of patients who were not exposed.MethodsWe retrospectively reviewed patients with advanced NSCLC treated with first-line chemo-IOs between 2018 and 2020 at the National Cancer Center Hospital. The patients were divided into two groups: those exposed to antibiotics within 30 days before induction therapy (ABx group) and those did not antibiotics (Non-ABx group). Propensity score matching was used to control for potential confounding factors. Clinical outcomes including progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared.ResultsOf 201 eligible patients, 21 were in the ABx group, and 42 were in the non-ABx group after propensity score matching. No differences in PFS or OS emerged between the two groups (ABx group vs. Non-ABx group) (PFS:7.0 months vs. 6.4 months, hazard ratio [HR] 0.89; 95% confidence interval [CI], 0.49–1.63, OS:20.4 months vs. 20.1 months, HR 0.87; 95% CI 0.44–1.71). The frequency of irAEs before propensity score matching was similar across any-grade irAEs (39.4% vs. 42.9%) or grade 3 or higher irAEs (9.1% vs. 11.3%).ConclusionAntibiotic-induced dysbiosis may not affect the efficacy of chemo-IOs in patients with advanced NSCLC.

Short-term supplementation with uncoated and encapsulated Enterococcus faecium affected growth performance, gut microbiome and intestinal barrier integrity in broiler chickens

Enterococcus faecium (E. faecium) is an alternative to antibiotics, while the probiotic effect of short-term application in mature broiler chickens remains unclear. In the current study, 48 Arbor Acres male broilers were chosen to investigate the effects of E. faecium on growth performance, the gut microbiome and intestinal health during the finishing period. Forty-eight birds were randomly allocated to 4 treatment groups that were fed a corn-soybean meal basal diet (Con), a basal diet supplemented with 1 g/kg amoxicillin (ABX), 5×106 CFU/g encapsulated E. faecium (cEF), or 5×106 CFU/g uncoated E. faecium (EF) from d 33 to 42. The results showed that 10 d of antibiotic treatment decreased the growth performance of the broilers (P < 0.05). The feed conversion ratio of the cEF and EF groups were lower than that of the Con group by 0.13 and 0.07, respectively (P > 0.05). The abundance of viable ileal and cecal E. faecium in the cEF group was greater than that in the EF group (P < 0.05), and both groups were markedly greater than those in the Con and ABX groups (P < 0.05). The ABX treatment decreased the Shannon and Chao1 indices of the cecal microbiota, while the dietary E. faecium treatment resulted in significant differences in the β diversity of the ileal and cecal microbiota (P < 0.05). Mantel correlation revealed that the ileal microbiota at the genus level was significantly correlated with the growth performance of broilers, with Lactobacillus, Bacillus and Escherichia-Shigella showing positive and strong correlations (P < 0.05). In the ileum, the crypt depth was lower in the cEF group than in the Con group, but the villi height-to-crypt depth ratio was greater in the cEF group than in the other groups (P = 0.037). However, the expression of the ZO-2 and Occludin genes was downregulated in the E. faecium-fed birds (P < 0.05). In the cecum, the acetate, butyrate and total SCFA levels were greater in the EF group (P < 0.05), while the propionate, isobutyrate and isovalerate levels were lower in the ABX group (P < 0.05). In summary, 10 d of dietary supplementation with E. faecium markedly increased colonization in mature broilers and potentially improved growth performance by modulating the ileal microbiota. Encapsulation techniques could enable a slow release of E. faecium in the intestine, thereby reducing the negative impacts of rapid expansion of E. faecium on the intestinal epithelium.

Prevotella intermedia boosts OSCC progression through ISG15 upregulation: a new target for intervention

PurposePeriodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects.MethodsIn this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups.ResultsCompared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4+ and CD8+ T cells.ConclusionIn conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.

Systematic review and meta-analysis of the management of acute uncomplicated diverticulitis: time to change traditional practice

BackgroundTo evaluate comparative outcomes of outpatient (OP) versus inpatient (IP) treatment and antibiotics (ABX) versus no antibiotics (NABX) approach in the treatment of uncomplicated (Hinchey grade 1a) acute diverticulitis.MethodsA systematic online search was conducted using electronic databases. Comparative studies of OP versus IP treatment and ABX versus NABX approach in the treatment of Hinchey grade 1a acute diverticulitis were included. Primary outcome was recurrence of diverticulitis. Emergency and elective surgical resections, development of complicated diverticulitis, mortality rate, and length of hospital stay were the other evaluated secondary outcome parameters.ResultsThe literature search identified twelve studies (n = 3,875) comparing NABX (n = 2,008) versus ABX (n = 1,867). The NABX group showed a lower disease recurrence rate and shorter length of hospital stay compared with the ABX group (P = 0.01) and (P = 0.004). No significant difference was observed in emergency resections (P = 0.33), elective resections (P = 0.73), development of complicated diverticulitis (P = 0.65), hospital re-admissions (P = 0.65) and 30-day mortality rate (P = 0.91). Twelve studies (n = 2,286) compared OP (n = 1,021) versus IP (n = 1,265) management of uncomplicated acute diverticulitis. The two groups were comparable for the following outcomes: treatment failure (P = 0.10), emergency surgical resection (P = 0.40), elective resection (P = 0.30), disease recurrence (P = 0.22), and mortality rate (P = 0.61).ConclusionObservation-only treatment is feasible and safe in selected clinically stable patients with uncomplicated acute diverticulitis (Hinchey 1a classification). It may provide better outcomes including decreased length of hospital stay. Moreover, the OP approach in treating patients with Hinchey 1a acute diverticulitis is comparable to IP management. Future high-quality randomised controlled studies are needed to understand the outcomes of the NABX approach used in an OP setting in managing patients with uncomplicated acute diverticulitis.

Abstract 2806: A single dose of perioperative cefazolin disrupts the gut microbiome and immunity in patients (pts) with early-stage melanoma

Abstract Background: Perioperative antibiotic prophylaxis is routinely utilized to reduce surgical site infections (SSIs). However, the rate of SSIs following a clean surgical procedure is &amp;lt;3%. Overuse of antibiotics is associated with potential adverse effects, including disruption of the composition and function of the native gut microbiota. Numerous studies have shown a negative impact of antibiotics on response and survival in patients with cancer treated with immune checkpoint blockade. The primary objective of this study was to determine the impact of a single dose of perioperative cefazolin on the gut microbiome and immunity. Methods: In this pilot trial (NCT04875728), 22 eligible pts diagnosed with clinical stage I or II melanoma undergoing wide excision with or without sentinel lymph node biopsy were enrolled between October 2021 and January 2023. Pts were randomized 1:1 to receive a single dose of cefazolin as standard-of-care (ABX, n=11) or no antibiotics (No ABX, n=11) at the time of surgery. Stool samples were collected before surgery, on post-operative day (POD) 14 and POD90 for metagenomic sequencing (WMS). Bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) collected at the same timepoints was performed and data processed using DESeq2, log-transformed, and standardized for subsequent analysis. Immune pathway enrichment scores were calculated using GSVA for each sample with gene lists from 3 immune pathways (ADAPTIVE_IMMUNE_SYSTEM, INNATE_IMMUNE_SYSTEM, and CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM) from REACTOME (https://reactome.org) and immune cell gene signatures from Danaher P et al, 2017. Results: Treatment with a single dose of perioperative cefazolin was associated with a decrease in the alpha diversity of the gut microbiome 2 weeks postoperatively in pts who received perioperative cefazolin versus those who did not receive antibiotics (p=0.057, R2=0.0526); this persisted to POD90 (p=0.021, R2=0.0948). WMS showed prominent and persistent decreases in Akkermansia muciniphila (POD14: Log2FC=-8.38, q&amp;lt;0.001) and Alistipes communis (POD90: Log2FC=-4.47, q&amp;lt;0.001) in the ABX group compared to No ABX, respectively. RNA-seq analysis of PBMCs from pts revealed differences in immune subsets at POD90 between ABX and No ABX groups including decreased IFN-γ signatures (p=0.02) in pts who received perioperative cefazolin. Conclusions: Perioperative antibiotic prophylaxis is associated with profound and persistent reduction in microbiome diversity and composition, particularly of bacterial species associated with protective metabolic and inflammatory effects. Further studies will seek to assess the functional impact of this reduction on the immune response in a murine model, evaluate the generalizability of our findings across broader cohorts of patients undergoing surgery, and apply these findings to guide clinical management decisions. Citation Format: Estefania Fernandez, Samuel Cass, Yongwoo D. Seo, Ashish V. Damania, Xiaolong Meng, Pranoti V. Sahasrabhojane, Jiun Sheng Liu, Wenbin Liu, Yulong Chen, Roland L. Bassett, Samuel Shelburne, Hsiu-Yin Chang, Kinjal R. Somaiya, Kristi S. Mungovan, Jared C. Malke, Brenna Matejka, Sarah B. Fisher, Anthony Lucci, Jeffrey E. Lee, Merrick I. Ross, Jeffrey E. Gershenwald, Padmanee Sharma, Nadim J. Ajami, Christina L. Roland, Jennifer A. Wargo, Emily Z. Keung. A single dose of perioperative cefazolin disrupts the gut microbiome and immunity in patients (pts) with early-stage melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2806.

Gut microbiota intervention attenuates thermogenesis in broilers exposed to high temperature through modulation of the hypothalamic 5-HT pathway

BackgroundBroilers have a robust metabolism and high body temperature, which make them less tolerant to high-temperature (HT) environments and more susceptible to challenges from elevated temperatures. Gut microbes, functioning as symbionts within the host, possess the capacity to significantly regulate the physiological functions and environmental adaptability of the host. This study aims to investigate the effects of gut microbial intervention on the body temperature and thermogenesis of broilers at different ambient temperatures, as well as the underlying mechanism involving the "gut-brain" axis.MethodsBroilers were subjected to gut microbiota interference with or without antibiotics (control or ABX) starting at 1 day of age. At 21 day of age, they were divided into 4 groups and exposed to different environments for 7 d: The control and ABX groups at room temperature (RT, 24 ± 1 °C, 60% relative humidity (RH), 24 h/d) and the control-HT and ABX-HT groups at high temperature (HT, 32 ± 1 °C, 60% RH, 24 h/d).Results The results demonstrated that the antibiotic-induced gut microbiota intervention increased body weight and improved feed conversion in broiler chickens (P < 0.05). Under HT conditions, the microbiota intervention reduced the rectal temperature of broiler chickens (P < 0.05), inhibited the expression of avUCP and thermogenesis-related genes in breast muscle and liver (P < 0.05), and thus decreased thermogenesis capacity. Furthermore, the gut microbiota intervention blunted the hypothalamic‒pituitary‒adrenal axis and hypothalamic–pituitary–thyroid axis activation induced by HT conditions. By analyzing the cecal microbiota composition of control and ABX chickens maintained under HT conditions, we found that Alistipes was enriched in control chickens. In contrast, antibiotic-induced gut microbiota intervention resulted in a decrease in the relative abundance of Alistipes (P < 0.05). Moreover, this difference was accompanied by increased hypothalamic 5-hydroxytryptamine (5-HT) content and TPH2 expression (P < 0.05).ConclusionsThese findings underscore the critical role of the gut microbiota in regulating broiler thermogenesis via the gut-brain axis and suggest that the hypothalamic 5-HT pathway may be a potential mechanism by which the gut microbiota affects thermoregulation in broilers.Graphical

Depletion of gut microbiota facilitates fibroblast growth factor 21-mediated protection against acute pancreatitis in diabetic mice.

Fibroblast growth factor 21 (FGF21), primarily secreted by the pancreas, liver, and adipose tissues, plays a pivotal role in regulating glucose and lipid metabolism. Acute pancreatitis (AP) is a common inflammatory disease with specific clinical manifestations. Many patients with diabetes present with concurrent inflammatory symptoms. Diabetes exacerbates intestinal permeability and intestinal inflammation, thus leading to the progression to AP. Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice. To investigate the potential protective role of FGF21 against AP in diabetic mice. In the present study, a mouse model of AP was established in diabetic (db)/db diabetic mice through ceruletide injections. Thereafter, the protective effects of recombinant FGF21 protein against AP were evaluated, with an emphasis on examining serum amylase (AMS) levels and pancreatic and intestinal inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-), and intestinal IL-1β]. Additionally, the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with AP. An antibiotic (Abx) cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformatics software package, was used to predict different pathways between the groups and to explore the potential mechanisms by which the gut microbiota influenced the protective effect of FGF21. The results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P < 0.01) and inflammatory factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ± 0.051, P < 0.01), and IL-1β (1.377 ± 0.069 vs 0.3328 ± 0.02542, P < 0.01) in diabetic mice with AP. Moreover, notable signs of recovery were observed in the pancreatic structure of the mice. The histologic evidence of inflammation in the small intestine, including edema and villous damage, was significantly alleviated. FGF21 also significantly altered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment with an Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed lower levels of serum AMS (0.9328 ± 0.075 vs 0.2249 ± 0.023, P < 0.01) and inflammatory factors (1.083 ± 0.12 vs 0.2799 ± 0.032, p < 0.01) than the FGF21 group. Furthermore, the FGF21 + Abx group exhibited diminished injury to the pancreatic and small intestinal tissues, accompanied by a significant decrease in blood glucose levels (17.50 ± 1.1 vs 9.817 ± 0.69 mmol/L, P < 0.001). These findings underscored the superior protective effects of the combination therapy involving an Abx cocktail with FGF21 over the FGF21 treatment alone in diabetic mice with AP. The gut microbiota composition across different groups was further characterized, and a differential expression analysis of gene functions was undertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confer therapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathway of n-acetylceramide degradation in the gut microbiota. This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing blood glucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effects of FGF21 are augmented when combined with the Abx cocktail.

Too Much of a Good Thing: Extended Duration of Gut Microbiota Depletion Reverses Protection From Experimental Autoimmune Uveitis.

Using the model of experimental autoimmune uveitis (EAU) induced by immunization with a retinal antigen, two studies have reported contradictory results on disease development following oral antibiotic treatment (ABX). We showed that long-term ABX did not affect EAU, but another study showed that short-term ABX was protective. We therefore studied the effects of ABX on EAU, gut microbiota, and host immune responses as a function of treatment duration. EAU-susceptible mice were treated orally with broad-spectrum antibiotics starting at least 10 weeks (long-term) or 1 week (short-term) before immunization until termination of the experiment. Gut microbiota were characterized by 16S amplicon sequencing, and host gut immune elements were studied phenotypically and functionally. Long-term ABX had no effect, whereas short-term ABX delayed EAU, as previously reported by us and others, respectively. Microbial sequencing revealed progressive reduction of gut microbiota that showed some differences in the two ABX groups. Interestingly, duration of ABX was associated with a gradual disappearance of the CD4+ and CD4+CD8+ subset of gut intraepithelial lymphocytes (IELs). This IEL subset is microbiota dependent and is absent in germ-free mice. Relative abundance of Lactobacillus reuteri correlated with the frequencies of CD4+CD8+ IELs. IELs suppressed antigen-specific activation of autoreactive T cells in culture. Gut microbiota may play dual roles in uveitis development: They promote EAU development but also help maintain IEL populations that have regulatory function against autoreactive T cells. We propose that the progressive loss of this population during long-term ABX reverses the EAU-ameliorating effects of microbiota depletion.

The gut microbiota contributes to changes in the host immune response induced by Trichinella spiralis.

The gut microbiota plays an important role in parasite-host interactions and the induction of immune defense responses. Trichinella spiralis is an important zoonotic parasite that can directly or indirectly interact with the host in the gut. Changes in the gut microbiota following infection with T. spiralis and the role of the gut microbiota in host immune defense against T. spiralis infection were investigated in our study. 16S rRNA sequencing analysis revealed that infection with T. spiralis can reduce the diversity of the gut microbiota and alter the structure of the gut microbiota during early infection, which was restored when the worm left the gut. Antibiotic treatment (ABX) and fecal bacterial transplantation (FMT) were used to investigate the role of the gut microbiota in the host expulsion response during infection with T. spiralis. We found that ABX mice had a higher burden of parasites, and the burden of parasites decreased after fecal bacterial transplantation. The results of flow cytometry and qPCR revealed that the disturbance of the gut microbiota affects the proportion of CD4+ T cells and the production of IL-4, which weakens Th2 responses and makes expulsion difficult. In addition, as the inflammatory response decreased with the changes of the microbiota, the Th1 response also decreased. The metabolomic results were in good agreement with these findings, as the levels of inflammatory metabolites such as ceramides were reduced in the ABX group. In general, T. spiralis infection can cause changes in the gut microbiota, and the presence or absence of microbes may also weaken intestinal inflammation and the expulsion of T. spiralis by affecting the immune response of the host.

Effects of Traditional Chinese Herbal Feed Additive on Production Performance, Egg Quality, Antioxidant Capacity, Immunity and Intestinal Health of Laying Hens.

Chinese herbs have been used as feed additives in animal production. This study investigated the effects of a Chinese herbal feed-additive (TCM, which contained Elsholtzia ciliate, Atractylodes macrocephala, Punica granatum pericarpium, and Cyperus rotundus) on the production performance, egg quality, antioxidant capacity, immunity, and intestinal health of Roman laying hens. A total of 720 28-week-old hens were randomly allotted to three groups with six replicates of forty hens each. The groups were fed a basal diet (CON group), a basal diet with 50 mg/kg zinc bacitracin (ABX group), or a basal diet with 400 mg/kg TCM (TCM group) for 56 days. The results showed that the TCM group increased egg production, egg mass, albumen height, and Haugh unit compared with the CON group (p < 0.05). There were no significant differences in egg weight, feed intake, feed conversion rate, and eggshell strength among all three groups (p > 0.05). Compared with the CON group, the TCM group enhanced the activities of glutathione peroxidase, total antioxidant capacity, and superoxide dismutase in serum and liver, and reduced malondialdehyde content (p < 0.05). The TCM also increased the levels of interleukin-2, interferon-γ, immunoglobulin A, immunoglobulin M, and immunoglobulin G, and decreased the levels of interleukin-6 and interleukin-8 compared with the CON group (p < 0.05). Furthermore, the TCM group increased jejunal goblet cell density and decreased ileal crypt depth and lymphocyte density compared with the CON group (p < 0.05). The results of 16S rRNA demonstrated that the TCM can change the diversity and composition of intestinal microbiota. At the phylum level, the abundance of Bacteroides increased while that of Firmicutes decreased in the TCM group (p > 0.05). At the genus level, the abundance of Lactobacillus, Rikenellaceae_RC9_gut_group, and Phascolarctobacterium increased while that of Bacteroides and unclassified_o__Bacteroidales decreased in the TCM group (p > 0.05). The effects of ABX were weaker than those of the TCM. In conclusion, the TCM has positive effects on production performance and the intestinal health of hens.

Tributyrin alleviates gut microbiota dysbiosis to repair intestinal damage in antibiotic-treated mice.

Tributyrin (TB) is a butyric acid precursor and has a key role in anti-inflammatory and intestinal barrier repair effects by slowly releasing butyric acid. However, its roles in gut microbiota disorder caused by antibiotics remain unclear. Herein, we established an intestinal microbiota disorder model using ceftriaxone sodium via gavage to investigate the effects of different TB doses for restoring gut microbiota and intestinal injury. First, we divided C57BL/6 male mice into two groups: control (NC, n = 8) and experimental (ABx, n = 24) groups, receiving gavage with 0.2 mL normal saline and 400 mg/mL ceftriaxone sodium solution for 7 d (twice a day and the intermediate interval was 6 h), respectively. Then, mice in the ABx group were randomly split into three groups: model (M, 0.2 mL normal saline), low TB group (TL, 0.3 g/kg BW), and high TB group (TH, 3 g/kg BW) for 11 d. We found that TB supplementation alleviated antibiotics-induced weight loss, diarrhea, and intestinal tissue damage. The 16S rRNA sequence analysis showed that TB intervention increased the α diversity of intestinal flora, increased potential short-chain fatty acids (SCFAs)-producing bacteria (such as Muribaculaceae and Bifidobacterium), and inhibited the relative abundance of potentially pathogenic bacteria (such as Bacteroidetes and Enterococcus) compared to the M group. TB supplementation reversed the reduction in SCFAs production in antibiotic-treated mice. Additionally, TB downregulated the levels of serum LPS and zonulin, TNF-α, IL-6, IL-1β and NLRP3 inflammasome-related factors in intestinal tissue and upregulated tight junction proteins (such as ZO-1 and Occludin) and MUC2. Overall, the adjustment ability of low-dose TB to the above indexes was stronger than high-dose TB. In conclusion, TB can restore the dysbiosis of gut microbiota, increase SCFAs, suppress inflammation, and ameliorate antibiotic-induced intestinal damage, indicating that TB might be a potential gut microbiota modulator.

Antibiotic-Induced Dysbiosis of the Gut Microbiota Impairs Gene Expression in Gut-Liver Axis of Mice.

Antibiotics can be a double-edged sword. The application of broad-spectrum antibiotics leads to the suppression of microorganisms in the human body without selective targeting, including numerous non-pathogenic microorganisms within the gut. As a result, dysbiosis of the gut microbiota can occur. The gut microbiota is a vast and intricate ecosystem that has been connected with various illnesses. Significantly, the gut and liver function in a closely coupled anatomical and physiological relationship referred to as the "gut-liver axis". Consequently, metabolites stemming from the gut microbiota migrate via the portal vein to the liver, thereby influencing gene expression and proper physiological activity within the liver. This study aimed to investigate the dysbiosis of gut microbiota ecology and the disruption of gene expression resulting from oral antibiotics and their subsequent recovery. In the experiment, mice were tube-fed neomycin (0.5 mg/mL) and ampicillin (1 mg/mL) for 21 days (ABX group) to conduct 16s rRNA sequencing. By simultaneously analyzing public datasets PRJDB6615, which utilized the same antibiotics, it was found that nearly 50% of the total microbiota abundance was attributed to the f__Lactobacillaceae family. Additionally, datasets GSE154465 and GSE159761, using the same antibiotics, were used to screen for differentially expressed genes pre-and post-antibiotic treatment. Quantitative real-time PCR was employed to evaluate gene expression levels before and after antibiotic treatment. It was discovered that oral antibiotics significantly disrupted gene expression in the gut and liver, likely due to the dysregulation of the gut microbiota ecology. Fecal microbiota transplantation (FMT) was found to be an effective method for restoring gut microbiota dysbiosis. To further enhance the restoration of gut microbiota and gene expression, an antioxidant, vitamin C, was added to the FMT process to counteract the oxidative effect of antibiotics on microorganisms. The results showed that FMTs with vitamin C were more effective in restoring gut microbiota and gene expression to the level of the fecal transplant donor.

1679-P: L-arginine Ameliorates Polycystic Ovary Syndrome and Attenuates Intestinal Oxidative Stress by Regulating Gut Microbiota

More than half of Polycystic ovary syndrome (PCOS) women are overweight or obese, and weight gain amplifies and worsens the symptoms of PCOS. Hence, it is essential to further understand and treat PCOS women with obesity. Therefore, this study tried to use a multi-omics approach that integrates the gut microbiome, serum metabolomics, serum transcriptomics, and clinical indicators to distinguish obese PCOS from obese non-PCOS women. The stool and blood samples from 33 obese PCOS patients and 30 obese control women were collected. The sequencing results suggested there were significant differences in gut microbiome and metabolites between obese PCOS women and obese women. Of which, the level of L-arginine (Arg) in obese PCOS patients was significantly lower than that in the control group and associated with gut microbiota alterations. Further correlation analysis between metabolite and clinical phenotype showed that Arg was significantly correlated with the clinical phenotype of obese PCOS patients. In this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) with a high-fat diet (HFD) to induce obese PCOS mice models for 3 weeks. PCOS mice were randomly divided into four groups: Arg group, Arg + antibiotic cocktail (ABX) group, PCOS group, and PCOS + ABX group. After 3 weeks of Arg supplementation, the estrous cycle, ovarian morphology, intestinal oxidative stress and intestinal barrier integrity were improved in Arg group PCOS mice, while testosterone levels and insulin resistance levels were decreased. However, these improvements were not observed in the Arg plus ABX group, suggesting that ABX-mediated depletion of the gut microbiome would eliminate these improvements. Then the 16s rRNA sequencing was performed to determine the gut microbiota of the four groups. The results showed that Arg can ameliorate reproductive characteristics of PCOS and attenuate intestinal oxidative stress by regulating gut microbiota. Disclosure D.Dilimulati: None. M.Cai: None. Y.Zhang: None. S.Qu: None. M.Zhang: None.