Search

Background: In placebo‐controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers. Methods: In a double‐blind, three‐way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8‐day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs. Key Results: Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmH2O (95% confidence interval [CI] 16.5–30.2, p < 0.001) during rest and with 22.5 cmH2O (95% CI 15.2–29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo. Conclusions & Inferences: An 8‐mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40‐mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone. [ABSTRACT FROM AUTHOR]

Following an extensive screening of reaction parameters such as the nature and amount of bases, Pd pre‐catalysts, ligands, additives, solvents and temperature range, we succeeded in developing a Heck reaction using N‐Boc‐allylamine and commercially available aryl bromides, capable of delivering a wide range of Boc‐protected trans‐cinnamylamines with 75–85 % regio‐ and stereoselectivity over other isomers. Optimisation of the Boc‐deprotection step and its work‐up procedure allowed for all minor isomers and impurities to be purged thus isolating pure trans‐cinnamylamines typically in 55–65 % yield without need for chromatography. We have successfully performed this chemistry in up to 5 g scale and demonstrated its usefulness by applying it to the synthesis of abamine, naftifine hydrochloride and a formal synthesis reboxetine mesylate. [ABSTRACT FROM AUTHOR]

About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely used effectively to treat depression for centuries, but when other medications were introduced, its use was discounted due to addiction and other hazards. In a series of previous studies, we evaluated the antinociceptive effects of eight antidepressant medications and their interaction with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of mianserin, mirtazapine, trazodone, venlafaxine, reboxetine, moclobemide, fluoxetine, or fluvoxamine to determine the effect of each drug in eliciting antinociception. When naloxone inhibited the antinociceptive effect, we further examined the effect of the specific opioid antagonists of each antidepressant drug. Mianserin and mirtazapine (separately) induced dose-dependent antinociception, each one yielding a biphasic dose-response curve, and they were antagonized by naloxone. Trazodone and venlafaxine (separately) induced a dose-dependent antinociceptive effect, antagonized by naloxone. Reboxetine induced a weak antinociceptive effect with no significant opioid involvement, while moclobemide, fluoxetine, and fluvoxamine had no opioid-involved antinociceptive effects. Controlled clinical studies are needed to establish the efficacy of the augmentation of opiate antidepressants in persons with treatment-resistant depression and the optimal dosage of drugs prescribed. [ABSTRACT FROM AUTHOR]

Background. Norepinephrine transporter inhibitors that can alter the level of neurotransmitter in the brain are used to treat neurological disorders. However, a number of studies have reported their limited significance as a result of their slow onset of action and moderate efficacy. Objectives. To determine the effects of norepinephrine reuptake inhibitors (NRIs), reboxetine and atomoxetine on schizophrenia and attention deficit hyperactivity disorder (ADHD). Materials and methods. Relevant articles published between 2000 and 2022 were searched in the MEDLINE, CINAHL (via Ebsco), Web of Science and Scopus databases. Among the various NRIs, studies concerning the 2 potent drugs - reboxetine and atomoxetine - were selected for analysis. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated, along with the exploration of heterogeneity and publication bias, using RevMan software. Results. A total of 14 eligible studies with a combined sample size of 970 patients were included. Using a random effects model, an OR of 0.55 (0.32-0.94), a Tau2 value of 0.23, a X2 value of 12.31, 8 degrees of freedom (df), an I2 of 35%, a Z value of 2.19, and a p-value of 0.03 were recorded for reboxetine. Atomoxetine had an OR of 0.35 (0.13-0.97), a Tau2 value of 0.58, a X2 value of 7.31, 4 df, an I2 of 45%, a Z value of 1.53, and a p-value of 0.04. All results were statistically significant with a low risk of publication bias, as was evident from the p-values >0.05 derived from the Egger's test and the Begg's test. These drugs provided comparable changes to control drugs in Hamilton Depression Rating Scale (HAM-D) scores, Positive and Negative Syndrome Scale (PANSS) scores and ADHD ratings. This confirms the efficacy of reboxetine for the treatment of schizophrenia and atomoxetine for the treatment of ADHD. Conclusions. The present meta-analysis suggests that NRIs are efficacious and therefore they are potential candidate drugs for the treatment of schizophrenia and ADHD. [ABSTRACT FROM AUTHOR]

Background There is limited experimentally controlled neuroimaging research available that could explain how dissociative states occur and which neurobiological changes are involved in acute post-traumatic dissociation. Aims To test the causal hypothesis that acute dissociation is triggered bottom-up by a selective noradrenergic-mediated increase in amygdala activation during the processing of autobiographical trauma memories. Method Women with post-traumatic stress disorder (n = 47) and a history of interpersonal childhood trauma underwent a within-participant, placebo-controlled pharmacological challenge paradigm (4.0 mg reboxetine versus placebo) employing script-driven imagery (traumatic versus neutral autobiographical memory recall). Script-elicited brain activation patterns (measured via functional magnetic resonance imagery) were analysed by means of whole-brain analyses and a pre-registered region of interest (i.e. amygdala). Results Self-reported acute dissociation increased significantly during trauma (versus neutral) recall but did not differ between pharmacological conditions. The pharmacological manipulation was also unsuccessful in eliciting increased amygdala activation following script-driven imagery in the reboxetine (versus placebo) condition. In the reboxetine condition, trauma retrieval resulted in similar activation patterns as in the placebo condition (e.g. elevated brain activation in the middle occipital gyrus and supramarginal gyrus), albeit with different peaks. Conclusions Current (null) findings cast doubt on the suggested role of the amygdala in subserving dissociative processing of trauma memories. Alternative pharmacological manipulation approaches (e.g. ketamine) and analysis techniques (e.g. event-related independent component analysis) might provide better insight into the spatiotemporal dynamics and network shifts involved in dissociative experiences and autobiographical trauma memory recall.

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Mental fatigue (MF) significantly affects both cognitive and physical performance. However, the precise mechanisms, particularly concerning neurotransmission, require further investigation. An implication of the role of dopamine (DA) and noradrenaline (NA) is stated, but empirical evidence for this theory still needs to be provided. To address this gap, we aim to investigate the role of brain neurotransmission in elucidating if, and how prolonged cognitive activity induces MF and its subsequent impact on cognitive performance., Methods: This study (registration number: G095422N) will adopt a randomized cross-over design with sixteen healthy participants aged 18-35 years. The sessions include a familiarization, two experimental (DA: 20mg Methylphenidate; NA: 8mg Reboxetine) conditions, and one placebo (lactose tablet: 10mg) condition. A 60-minute individualized Stroop task will be used to investigate whether, and how the onset of MF changes under the influence of reuptake inhibitors. Attention and response inhibition will be assessed before and after the MF-inducing task using a Go/NoGo task. The integration of physiological (electroencephalography, heart rate), behavioral (attention, response inhibition), and subjective indicators (scales and questionnaires) will be used to detect the underlying mechanisms holistically. Data analysis will involve linear mixed models with significance at p<0.05., Discussion: The integration of diverse techniques and analyses offers a comprehensive perspective on the onset and impact of MF, introducing a novel approach. Future research plans involve extending this protocol to explore the connection between brain neurotransmission and physical fatigue. This protocol will further advance our understanding of the complex interplay between the brain and fatigue., Competing Interests: The authors declared that no competing interests exist., (Copyright: © 2024 Arenales Arauz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Urethral closure function is essential for urinary continence in women and decreased urethral pressure is associated with stress urinary incontinence (SUI). For decades, the effects of serotonergic drugs on central neural control of urethral closure have been investigated and discussed. Epidemiological studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is associated with SUI. However, the literature findings are conflicting. This study aimed to evaluate citalopram's effect on opening urethral pressure (OUP) in healthy women. Methods: We conducted a randomized, double‐blind, placebo‐ and active‐controlled crossover study in 24 healthy women. On three study days, which were separated by 8 days of washout, the subjects received single doses of either 40 mg citalopram (and placeboreboxetine), 8 mg reboxetine (and placebocitalopram), or two placebos. Study drugs were administered at a 1‐h interval due to a difference in estimated time to peak plasma concentration (tmax). We measured OUP with urethral pressure reflectometry under both resting and squeezing conditions of the pelvic floor at estimated tmax for both study drugs (one timepoint). Results: Compared to placebo, citalopram increased OUP by 6.6 cmH20 (95% confidence interval [CI] 0.04–13.1, p = 0.048) in resting condition. In squeezing condition, OUP increased by 7.1 cmH20 (95% CI: 1.3–12.9, p = 0.01). Reboxetine increased OUP by 30.0 cmH20 in resting condition compared to placebo (95% CI: 23.5–36.5, p < 0.001), and 27.0 cmH20 (95% CI: 21.2–32.8, p < 0.001) in squeezing condition. Conclusion: Citalopram increased OUP slightly compared to placebo suggesting that SSRI treatment does not induce or aggravate SUI. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors report no conflicts of interest.

Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

Background Noradrenaline has an important role as a neuromodulator of the central nervous system. Noradrenergic enhancement was recently shown to enhance glutamate-dependent cortical facilitation and long term potentiation-like plasticity. As cortical excitability and plasticity are closely linked to various cognitive processes, here we aimed to explore whether these alterations are associated with respective cognitive performance changes. Specifically, we assessed the impact of noradrenergic enhancement on motor learning (serial reaction time task), attentional processes (Stroop interference task), and working memory performance (n-back letter task). Methods The study was conducted in a cross-over design. Twenty-five healthy humans performed the respective cognitive tasks after a single dose of the noradrenaline reuptake inhibitor reboxetine or placebo administration. Results The results show that motor learning, attentional processes, and working memory performance in healthy participants were improved by reboxetine application compared with placebo. Conclusions The results of the present study thus suggest that noradrenergic enhancement can improve memory formation and executive functions in healthy humans. The respective changes are in line with related effects of noradrenaline on cortical excitability and plasticity. [ABSTRACT FROM AUTHOR]

Identifying additional noninvasive biomarkers for affective disorders, such as unipolar major depressive disorder (MDD) and bipolar disorder (BD), could aid in the diagnosis and treatment of these prevalent and debilitating neuropsychiatric conditions. One such candidate biomarker is the loudness dependence of the auditory evoked potential (LDAEP), an event-related potential that measures responsiveness of the auditory cortex to different intensities of sound. The LDAEP has been associated with MDD and BD, including therapeutic response to particular classes of antidepressant drugs, while also correlating with several other neuropsychiatric disorders. It has been suggested that increased values of the LDAEP indicate low central serotonergic neurotransmission, further implicating this EEG measure in depression. Here, we briefly review the literature on the LDAEP in affective disorders, including its association with serotonergic signaling, as well as with that of other neurotransmitters such as dopamine. We summarize key findings on the LDAEP and the genetics of these neurotransmitters, as well as prediction of response to particular classes of antidepressants in MDD, including SSRIs versus noradrenergic agents. The possible relationship between this EEG measure and suicidality is addressed. We also briefly analyze acute pharmacologic studies of serotonin and/or dopamine precursor depletion and the LDAEP. In conclusion, the existing literature suggests that serotonin and norepinephrine may modulate the LDAEP in an opposing manner, and that this event-related marker may be of use in predicting response to chronic treatment with particular pharmacologic agents in the context of affective disorders, such as MDD and BD, including in the presence of suicidality. [ABSTRACT FROM AUTHOR]

Major depression (MD) is a frequent comorbidity in alcohol use disorder (AUD) patients. Antidepressant prescription is often limited by poor clinical outcomes or unwanted side effects in comorbid AUD‐MD patients. Recent studies suggest that abrupt cessation of selective serotonin reuptake inhibitors antidepressant treatment increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) is not known. Here, we report that interruption of subchronic (14 days) treatment with the SNRIs reboxetine (15 mg/kg/day intraperitoneally) resulted in escalation of ethanol intake when the animals resume alcohol self‐administration. This effect of reboxetine treatment cessation was associated with a profound deactivation of the endocannabinoid/acylethanolamide signaling system in the prefrontal cortex but not in the dorsal hippocampus, as reflected by the decrease in the protein expression of the cannabinoid CB1 receptor, the PPARα receptor, the 2‐arachidonoylglycerol synthesizing enzymes DAGLα and DGALβ, and the endocanabinoid degrading enzyme MAGL. This was associated with dysregulation of the expression of glutamic acid receptors GluN1, GluA1, and mGlu5 in the medial prefrontal cortex and the dorsal hippocampus of the animals exposed to reboxetine. The present results further support the idea that abrupt cessation of antidepressant therapy along alcohol deprivation time can boost alcohol intake after relapse through mechanisms associated with endocannabinoid/glutamate signaling dysregulation. This finding might be relevant for patients suffering AUD/MD comorbidity where antidepressant therapy must be monitored with caution for avoiding unwanted side effects if adherence to the treatment is not fully achieved. [ABSTRACT FROM AUTHOR]

Background: Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition increases synaptic norepinephrine reuptake, which may be able to prevent hypotension, bradycardia, and syncope.Objective: The objective of this systematic review was to evaluate the ability of 3 NET inhibitors-reboxetine, sibutramine, and atomoxetine-to prevent head-up tilt-induced vasovagal outcomes in healthy participants and patients with VVS.Methods: Relevant studies were identified from Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature without language restriction from database inception to August 2019. All randomized controlled trials comparing the benefit of a NET inhibitor vs placebo in adult populations were selected for review and meta-analysis.Results: Four studies (101 participants) met inclusion criteria. The mean study size was 25 (range 11-56) participants. NET inhibition reduced the likelihood of vasovagal reactions marked by hypotension and bradycardia in healthy participants during head-up tilt testing (relative risk 0.15; 95% confidence interval 0.04-0.52; P = .003). This relative risk reduction also occurred in patients with VVS during head-up tilt when given atomoxetine (relative risk 0.49; 95% confidence interval 0.28-0.86; P = .01). This was achieved through heart rate compensation with NET inhibition toward the end of tilt testing (106 ± 32 beats/min vs 60 ± 22 beats/min; P < .001), which in turn preserved cardiac output and mean arterial pressure (71 ± 20 mm Hg vs 43 ± 13 mm Hg; P < .001) in the absence of significantly increased systemic vascular resistance.Conclusion: NET inhibition prevents severe vasovagal reactions and syncope induced by head-up tilt testing in both healthy participants and patients with VVS. Pharmacological NET inhibition is a promising potential treatment of recurrent syncope. [ABSTRACT FROM AUTHOR]

Rationale: Current data indicate that the noradrenergic system plays a critical role in neuropathic pain treatment. Notably, drugs that directly affect this system may have curative potential in neuropathy-associated pain. Objectives: The aim of this study was to evaluate the potential therapeutic efficacy of reboxetine, a potent and selective noradrenaline reuptake inhibitor, on hyperalgesia and allodynia responses in rats with experimental diabetes. Furthermore, mechanistic studies were performed to elucidate the possible mode of actions. Methods: Experimental diabetes was induced by a single dose of streptozotocin. Mechanical hyperalgesia, mechanical allodynia, thermal hyperalgesia, and thermal allodynia responses in diabetic rats were evaluated by Randall–Selitto, dynamic plantar, Hargreaves, and warm plate tests, respectively. Results: Reboxetine treatment (8 and 16 mg/kg for 2 weeks) demonstrated an effect comparable to that of the reference drug, pregabalin, improving the hyperalgesic and allodynic responses secondary to diabetes mellitus. Pretreatment with phentolamine, metoprolol, SR 59230A, and atropine did not alter the abovementioned effects of reboxetine; however, the administration of α-methyl-para-tyrosine methyl ester, propranolol, ICI-118,551, SCH-23390, sulpiride, and naltrindole significantly inhibited these effects. Moreover, reboxetine did not induce a significant difference in the rat plasma glucose levels. Conclusions: Our findings indicate that the antihyperalgesic and antiallodynic effects of reboxetine are mediated by the catecholaminergic system; β2-adrenoceptors; D1-, D2/D3-dopaminergic receptors; and δ-opioid receptors. The results suggest that this analgesic effect of reboxetine, besides its neutral profile on glycemic control, may be advantageous in the pharmacotherapy of diabetic neuropathy–induced pain. [ABSTRACT FROM AUTHOR]

Background Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. Aim The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). Methods Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. Results Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: −0.47 [95% CI: −0.87, −0.07], p=0.02; I2 =82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: −3.83 kg, p=0.04; I2 =92%) and body mass index (WMD: −2.23 kg/m2 , p=0.04; I2 =95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. Conclusion Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia. [ABSTRACT FROM AUTHOR]

The reduction of brain noradrenaline levels is associated to the initiation of Alzheimer's disease and contributes to its progression. This seems to be due mainly to the anti-neuroinflammatory actions of noradrenaline. The analysis of noradrenaline effects on brain cells demonstrates that it also regulates the production of the chemokine CCL2. In the present study, we analyzed the effect of the selective noradrenaline reuptake inhibitor, reboxetine, on the inflammatory and neurodegenerative alterations present in 5xFAD mice, and how the genetic removal of CCL2 affects reboxetine actions. We observed that the removal of CCL2 reduced the memory impairments in 5xFAD mice as well as the neuroinflammatory response, the accumulation of amyloid beta plaques, and the degeneration of neurons in the brain cortex. The administration of reboxetine with osmotic pumps for 28 days also resulted in anti-inflammatory and neuroprotective changes in 5xFAD mice, even in the absence of CCL2. Yet, 6-month-old CCL2KO mice presented a significant degree of neuroinflammation and neuronal damage. These findings indicate that reboxetine treatment prevents the brain alterations caused by prolonged overproduction of amyloid beta, being these effects independent of CCL2, which is a mediator of the damage caused by amyloid beta in the brain cortex, but necessary for the prevention of the development of neurodegeneration in normal healthy conditions. [ABSTRACT FROM AUTHOR]

Depression is one of the most common mental disorders in the world that negatively affects the daily functioning of patients. Numerous studies are currently being conducted to examine the antidepressant potential of innovative synthetic compounds and herbal substances. Yacon, Smallantchus sonchifolius, belongs to plants with numerous health-beneficial properties. Yacon-based products are regarded as a functional food. In our study, we attempted to check whether administration of Yacon tuber extract would have an antidepressant effect in the forced swim test (FST) in mice and whether its intake could influence the activity of conventional antidepressant drugs with different mechanisms of action, i.e., imipramine hydrochloride, fluoxetine hydrochloride, and reboxetine mesylate. The spontaneous locomotor activity of the tested mice was also investigated to eliminate any false-positive results. We demonstrated that an intragastric administration of the Yacon tuber extract at a dose of 100 mg/kg induced the antidepressant-like behavior in the FST in mice and that a combined administration of the sub-effective doses of the Yacon extract (50 mg/kg) with imipramine hydrochloride (7.5 mg/kg), fluoxetine hydrochloride (20 mg/kg), or reboxetine mesylate (5 mg/kg) significantly reduced the immobility time of animals in this behavioral test. The obtained results were not affected by the increased locomotor activity of the tested subjects. In conclusion, our findings suggest that Yacon tuber extract is promising as an alternative mood-improving product since it possesses an antidepressant potential and it can acts synergistically with conventional antidepressant drugs.

Antidepressants are drugs commonly used in clinical settings. However, there are very limited studies on the effects of these drugs on the gut microbiota. Herein, we evaluated the effect of reboxetine (RBX), a selective norepinephrine (noradrenaline) reuptake inhibitor (NRI), on gut microbiota in both diabetic and non-diabetic rats. This is the first report of relation between reboxetine use and the gut microbiota to our knowledge. In this study, type-1 diabetes induced by using streptozotocin (STZ) and RBX was administered to diabetic rats and healthy controls for 14 days. At the end of the treatment, stool samples were collected. Following DNA extraction, amplicon libraries for the V3-V4 region were prepared and sequenced with the Illumina Miseq platform. QIIME was used for preprocessing and analysis of the data. As a result, RBX had a significant effect on gut microbiota structure and composition in diabetic and healthy rats. For example, RBX exposure had a pronounced microbial signature in both groups, with a low Firmicutes/Bacteroidetes ratio and low Lactobacillus levels. While another abundance phylum after exposure to RBX was Proteabacteria, other notable taxa in the diabetic group included Flavobacterium, Desulfovibrionaceae, Helicobacteriaceae, Campylobacterales, and Pasteurellacae when compared to the untreated group.