Search Results (237)

To investigate whether Echinacea purpurea polysaccharides (EPP) alleviate inflammatory bowel disease (IBD) by modulating gut microbiota, we utilized a mixed antibiotic (ABX)-induced gut dysbiosis model and a co-housing model in rats. ABX treatment severely reduces microbial richness and functional diversity, decreasing SCFA-producing bacteria and impairing the anti-inflammatory effect of SCFA-mediated EPP. Without ABX, EPP significantly ameliorates IBD symptoms and colonic pathology damage in rats, reduces the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) (p < 0.05), inhibits the activation of the TRAF6/NF-κB signaling pathways, and reverses gut microbiota imbalance by partially restoring Bacteroidetes abundance and reducing Firmicutes levels. Among co-housed rats, the EPP-treated group exhibited significantly lower Disease Activity Index (DAI) scores, serum levels of pro-inflammatory factors, and colonic expression of pro-inflammatory pathway-related gene (TRAF6, STAT3) (p < 0.05) without ABX. 16S rRNA gene sequencing revealed a significant reduction in Firmicutes abundance (p < 0.05) alongside significant increases in Bacteroidetes and Actinobacteria abundances, accompanied by elevated levels of acetic acid and propionic acid (p < 0.05). These findings suggest recipient mice restored microbial function and acquired IBD-regulating ability post-microbial exchange. EPP alleviates IBD-related pathological injury by inhibiting the JAK2/STAT3 and TRAF6/NF-κB signaling pathways, with its therapeutic mechanism intricately linked to the microbiota–metabolite–host axis. Full article

Protein-losing enteropathy (PLE) is a spectrum of gastrointestinal disorders in which protein loss occurs through the gastrointestinal tract. One of the underlying causes is chronic inflammatory enteropathy (CIE). Conventional therapies for CIE often include diet, immunosuppressives, anti-microbials, probiotics, and, recently, fecal microbial transplantation (FMT). This case report highlights the use of lyophilized material-based FMT through oral capsules and enema in a dog with PLE and concurrent protein-losing nephropathy (PLN). The patient initially had a significantly increased dysbiosis index (DI) and required repeated FMT treatments, resulting in a positive clinical response through improvement in body weight, serum albumin concentrations, fecal scores, and normalization of the DI over time. To maintain clinical responses, FMT had to be performed monthly. Approximately 1 year after starting FMT therapy, the patient then developed an episode of acute hemorrhagic diarrhea syndrome (AHDS) associated with netF-gene-encoding Clostridium perfringens strains, after which the DI became abnormal again. The patient responded clinically well to monthly FMT treatments again, but it took several months for normalization of the DI after the AHDS episode. In summary, this case report highlights the continued use of adjunct lyophilized FMT in a dog with PLE resulting in improved clinical control over time. Full article

Background: Gastrointestinal discomfort affects up to 70% of individuals with spinal cord injury (SCI), largely due to gut dysbiosis caused by altered transit time and reduced gastrointestinal motility from autonomic disruption. Emerging evidence links prebiotics and probiotics to improved microbiome balance and reduced inflammation, yet data in SCI remain limited. Methods: Individuals aged ≥ 18 years, with a chronic SCI (≥1 year) experiencing significant gastrointestinal symptoms, will be invited to participate in this single-center randomized controlled crossover trial. Persons currently taking antibiotics, who have relevant eating or digestive disorders, or who have undergone a recent diet change will be excluded from the study. Participants will be randomized (1:1) into two groups. The first group will take a probiotic (Biotics-G, Burgerstein AG, Rapperswil-Jona, Switzerland) supplement for eight weeks, then after a four-week washout period, they will take a prebiotic (Oat Bran, Naturaplan, manufactured by Swissmill, Zurich, Switzerland) supplement for another eight weeks. The second group will receive the supplements in reverse order. The primary outcome is the Gastrointestinal Quality of Life Index, a questionnaire to assess quality of life related to gastrointestinal disorders. Secondary outcomes consist of gastrointestinal transit time, inflammatory blood markers, and gut microbiome composition. Ethics: The study will be conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee for Northwest/Central Switzerland (EKNZ, ID: 2025-00238, 24.02.2025, Version 2.0). The study is registered at ClinicalTrials.gov (ID: NCT06870331, 02.04.2025). Written informed consent will be obtained from all participants involved in the study. Full article

Overwinter Syndrome (OWS) affects grass carp (Ctenopharyngodon idellus) aquaculture in China, causing high mortality and economic losses under low temperatures. Failure of antibiotic therapies shows limits of the ‘low–temperature–pathogen’ model and shifts focus to mucosal barrier dysfunction and host–microbiome interactions in OWS. We compared healthy and diseased grass carp collected from the same pond using histopathology, transcriptomics, proteomics, and metagenomics. This integrated approach was used to characterize intestinal structure, microbial composition, and host molecular responses at both taxonomic and functional levels. Results revealed a three-layer barrier failure in OWS fish: the physical barrier was compromised, with structural damage and reduced mucosal index; microbial dysbiosis featured increased richness without changes in diversity or evenness, and expansion of the virobiota, notably uncultured Caudovirales phage; and mucosal immune dysregulation indicated loss of local immune balance. Multi-omics integration identified downregulation of lysosome-related and glycosphingolipid biosynthesis pathways at transcript and protein levels, with disrupted nucleotide metabolism. Overall gut microbial richness, rather than individual taxa abundance, correlated most strongly with host gene changes linked to immunity, metabolism, and epithelial integrity. Although biological replicates were limited by natural outbreak sampling, matched high-depth multi-omics datasets provide exploratory insights into OWS-associated intestinal dysfunction. In summary, OWS entails a cold-triggered breakdown of intestinal barrier integrity and immune homeostasis. This breakdown is driven by a global restructuring of the gut microbiome, which is marked by increased richness, viral expansion, and functional shifts, ultimately resulting in altered host–microbe crosstalk. This ecological perspective informs future mechanistic and applied studies for disease prevention. Full article

Lipodystrophies are rare syndromes characterized by partial or complete loss of subcutaneous adipose tissue leading to ectopic lipid deposition, insulin resistance, and the same metabolic derangements observed in obesity. Given the role of gut microbiota in metabolic disorders, we investigated whether its signature in obesity may be mirrored by that found in lipodystrophies, possibly contributing to their overlapping metabolic abnormalities. In this cross-sectional study, we included 8 individuals with lipodystrophy (LD), 16 individuals with obesity (Ob)—further categorized into 8 metabolically healthy (MHO) and 8 metabolically unhealthy (MUHO)—and 16 normal-weight controls (N). We assessed clinical and metabolic characteristics and performed 16S rRNA sequencing and bioinformatic analyses on fecal samples to characterize the gut microbiome. LD presented significantly lower body mass index (BMI) and waist circumference than Ob, but, from a metabolic perspective, LD showed similarity with MUHO and presented significantly lower levels of HDL-C and higher triglycerides compared to both N and MHO. Gut microbiota analysis revealed reduced α-diversity in LD, MHO and MUHO compared to N, whilst β-diversity and Firmicutes/Bacteroidetes ratio differences were not significant. At the phylum level, differential abundance analysis revealed that LD individuals exhibit similar microbial characteristics to MUHO and higher Verrucomicrobiota levels compared to MHO. The shared gut microbiota signature suggests another potential unexplored link between the pathogenesis of metabolic complications in lipodystrophies and obesity, providing novel insights into the complex interplay between dysbiosis and adiposopathy. Larger longitudinal studies are needed to explore the role of specific taxa and for a more precise characterization of different lipodystrophy subtypes. Full article

Background/Objectives: The study investigated the potential of mixed fruits and berries (MFB) as a dietary intervention to mitigate cafeteria (CAF) diet-induced gut microbiome dysbiosis and hepatic dysfunction associated with metabolic syndrome and steatohepatitis (MASH) in an adolescent rat model. Methods: Forty-eight adolescent male Sprague-Dawley rats (n = 3 cages per group (two rats per cage)) were divided into eight experimental groups, where NC received the normal AIN-93G basal diet, PC received the CAF diet and normal AIN-93G basal diet, T₁ and T₂ received MFB supplementation (3% and 6% levels) without CAF exposure, P₁ and P₂ received a MFB (3% and 6% levels) supplementation initiated at the onset of CAF feeding, and I₁ and I₂ received MFB supplementation initiated 2 weeks after CAF feeding. After 6 weeks, cecal 16S rRNA, hepatic histopathology, Oil Red O staining, and metabolic dysfunction-associated steatotic liver disease (MASLD)-related biomarkers (liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) were analyzed. Results: AST: ALT ratio was the highest in the PC group (3.63, p < 0.05) compared to the MFB groups. Oil Red O staining showed lower hepatic lipid accumulation, and histological analysis demonstrated a marked reduction in portal inflammatory cell infiltration in MFB. Alpha diversity (Simpson Index) decreased in PC (Kruskal–Wallis, p = 0.043). CAF increased Lactobacillus johnsonii (+75%, p < 0.05), while reducing L. murinus and L. intestinalis (~90%, p < 0.05). MFB supplementation restored Bifidobacterium Pseudolongum and increased Akkermansia muciniphila levels in the P₂, I₁, and I₂ groups (~20-fold, p < 0.05). Bacteroides dorei was present in all groups except the PC group. These bacteria presented a positive correlation with key SCFAs. Conclusions: The results from this study indicated that MFB supplementation modulated gut microbiota composition and enhanced SCFA production, thereby strengthening intestinal barrier integrity and reducing gut-derived inflammation. Collectively, these effects attenuated hepatic lipid accumulation and inflammation, highlighting the potential of MFB to restore gut–liver axis homeostasis disrupted by CAF-induced dysbiosis in adolescent rats. Full article

Background/Objectives: Gut dysbiosis in Chronic Fatigue Syndrome (CFS) drives low-grade inflammation and shifts tryptophan metabolism toward neurotoxic pathways. The causal link between bacterial translocation, kynurenine pathway dysregulation, and symptom severity remains under-defined. We evaluated the impact of a high-concentration multi-strain probiotic on the “gut-kynurenine axis” and clinical status in CFS patients with co-morbid IBS-U and confirmed dysbiosis. Methods: Forty female patients with confirmed dysbiosis (GA-map™ Dysbiosis Index > 2) received the CDS22 formula (450 billion CFU/day) for 12 weeks. We compared urinary tryptophan metabolite profiles (LC-MS/MS), gut dysbiosis markers (3-indoxyl sulfate), and fatigue severity (FSS) against 40 age-matched healthy controls. Results: Baseline analysis revealed profound metabolic perturbations: elevated bacterial proteolytic markers (3-IS), substrate depletion (low tryptophan), and a neurotoxic signature (high quinolinic acid [QA], low kynurenic acid [KYNA]). Following the intervention, fatigue scores declined by 40.3%, with 97.5% of patients reaching the remission threshold (FSS < 36). Biochemically, 3-IS levels decreased to the range observed in healthy controls and attenuated xanthurenic acid levels. Although absolute QA concentrations remained elevated compared to controls, the neuroprotective KYNA/QA ratio increased significantly (+45%). Increased systemic tryptophan availability correlated directly with clinical symptom reduction (Spearman’s rho = −0.36, p = 0.024). Conclusions: The CDS22 formulation was associated with a restoration of intestinal eubiosis and functional tryptophan partitioning. Clinical remission coincides with a metabolic shift favoring neuroprotection (increased KYNA/QA ratio), validating the gut–kynurenine axis as a modifiable therapeutic target. Peripheral metabolic improvement relative to the healthy baseline appeared sufficient for symptom relief in this specific phenotype, despite incomplete clearance of neurotoxic metabolites. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which barrier impairment, immune dysregulation, and gut–skin dysbiosis intersect, prompting growing interest in probiotics as microbiota-modulating adjuncts. We conducted a narrative review of peer-reviewed articles indexed in PubMed, Scopus, and Google Scholar, restricted to publications from 1 January 2018 to 31 October 2025 (searches last run in December 2025). Eligible evidence included randomized controlled trials (RCTs), observational studies, and mechanistic or conceptual reviews addressing microbiome alterations and microbiota-modulating interventions in AD. Most pediatric RCTs using multistrain, Lactobacillus-dominant formulations (often combined with Bifidobacterium) reported modest improvements in AD severity and pruritus and in selected barrier- and inflammation-related biomarkers. However, direct cutaneous microbiome “restoration” outcomes were reported in a minority of studies, and most clinical evidence relies on clinical endpoints and gut–skin axis plausibility rather than longitudinal skin microbiome readouts. Single-strain regimens showed inconsistent effects, and evidence in adolescents and adults remained heterogeneous. Mechanistically, probiotics may enhance short-chain fatty acid (SCFA) signaling, dampen toll-like receptor 2/4 (TLR2/4)-nuclear factor kappa B (NF-κB) activation, and promote interleukin-10 (IL-10)- and transforming growth factor-β (TGF-β)-driven tolerance. Probiotics are a biologically plausible adjunct targeting the gut–skin axis in AD and are generally well tolerated; however, heterogeneity across trials, limited follow-up, inconsistent adverse-event reporting, and scarce skin microbiome endpoints preclude firm clinical recommendations. Full article

Background: Amoxicillin, clindamycin and azithromycin are the most frequently prescribed antibiotics for odontogenic infections, but their comparative effects on gut microbiota and intestinal homeostasis remain insufficiently understood. Disruption of gut microbiota, short-chain fatty acid (SCFA) production, and mucosal barrier integrity may contribute to gastrointestinal symptoms. We aimed to compare the impacts of these antibiotics on gut microbiota, SCFA levels, and colonic goblet cells. Methods: C57BL/6N mice were treated with oral amoxicillin, clindamycin, or azithromycin at clinically relevant dosages. Cecal index, fecal water content, and diarrhea index were assessed during treatment and recovery. Gut microbiota composition and absolute bacterial abundance were determined using 16S rRNA amplicon absolute quantification sequencing. SCFAs in cecal contents were quantified by gas chromatography–mass spectrometry. Goblet cell abundance and Muc2 mRNA expression in colon tissues were evaluated using Alcian blue staining and RT-PCR. Results: Amoxicillin caused moderate increases in cecal index, reduced Ligilactobacillus abundance, increased Escherichia-Shigella, lowered SCFA levels, and decreased goblet cells and Muc2 expression, with partial recovery after two weeks. Clindamycin induced more severe dysbiosis, including sustained Proteobacteria expansion, persistent loss of beneficial taxa, 86–90% reduction in SCFA production, and lasting decreases in goblet cells and Muc2 expression without recovery during the observation period. Azithromycin caused mild and reversible changes across all parameters. Conclusions: Among the three antibiotics, azithromycin had the least detrimental effects on gut microbiota, SCFA production, and mucosal barrier function, whereas clindamycin caused profound and persistent intestinal disruption. These findings provide comparative evidence to inform antibiotic selection in clinical practices. Full article

Background/Objectives: End-stage chronic kidney disease (ESKD) represents a complex condition that also impacts oral health. This pilot study evaluates and compares some approaches to oral health assessment and aims to define the specific oral features common in adolescents with ESKD. Methods: A total of 50 children aged 12 to 17 years were examined, including 30 adolescents with ESKD (Group 1) and 20 adolescents without urinary pathology (Group 2). The decayed, missing, filled teeth (DMFT) index, oral hygiene index-simplified, papillary marginal attached index, and periodontal index were used for dental and periodontal assessment. The Milwaukee PH56 device was used to determine salivary pH. Oral microbiota was analyzed by chromatography–mass spectrometry and polymerase chain reaction detection of periodontopathogenic bacteria. Salivary and gingival crevicular fluid (GCF) biomarkers (IL-1β, TNF-α, IL-8, VEGF, sIgA) and total antioxidant capacity (TAC) were determined using an enzyme-linked immunosorbent assay. Results: DMFT did not differ between the groups. Periodontal indices in Group 1 were increased compared to Group 2 (p < 0.0001). Salivary pH in Group 1 was slightly alkaline; in Group 2, it was slightly acidic (p < 0.0001). Oral dysbiosis and periodontopathogenic bacteria were found in ESKD adolescents. Salivary IL-1β, TNF-α, VEGF, and IL-1β in GCF were elevated in Group 1 compared to Group 2 (p < 0.05). TNF-α, IL-8, and VEGF in GCF and TAC in both fluids were lower in Group 1 compared to Group 2 (p < 0.0001). Salivary IL-8 and sIgA in both saliva and GCF did not differ between the groups. Conclusions: ESKD adolescents had poor oral hygiene and significant oral dysbiosis including periodontopathogenic bacteria. Evaluation of biomarkers in saliva and GCF allowed us to vindicate inflammation, dysbiosis severity, and periodontal diseases. Full article

Background/Objectives: The pathogenesis of ulcerative colitis (UC) is complex, and there is an urgent need for effective therapeutic agents with low side effects. Recent studies highlight the critical roles of abnormal bile acid (BA) metabolism and gut microbiota dysbiosis in UC progression. However, there is a significant knowledge gap about the relation between BA and gut microbiota. The BA derivative T3K exerts good anti-UC effect, and its mechanism is still unknown. In this study, we investigate how its anti-UC mechanism is involved in the modulation of the gut microbiota-BA axis and BA metabolism. Methods: Gene expression microarray GSE92415 of UC from the Gene Expression Omnibus was used to analyze BA metabolism. DSS-induced colitis mouse model, Caco-2 and IEC6 cells were used to confirm the anti-UC of T3K using intestinal permeability assay with FITC, Western-blot, immunohistochemical staining, immunofluorescenc and so on in vitro and in vivo. The changes in bile acid and microbiota were measured by 16S rRNA sequencing and bile acid analysis combined with pseudo-germ-free (PGF) models and fecal microbiota transplantation (FMT). Results: T3K demonstrated strong therapeutic effects, including reduced weight loss, lower disease activity index (DAI), and increased colon length. T3K also enhanced the expression of Occludin and Mucin2, and restored gut barrier integrity. Furthermore, T3K improved intestinal dysbiosis and abnormal BA metabolism in colitis mice. Through PGF models and FMT, we confirmed that T3K modulates BA metabolism via the gut microbiota. T3K specifically promotes the growth of beneficial bacteria, such as Akkermansia muciniphila, increases levels of hydrophilic BAs like muricholic acid (MCA), lithocholic acid (LCA) and its derivatives isoLCA and then repairs damaged intestinal mucosa. Conclusions: Bile acid derivative T3K, as a potential anti-UC candidate, effectively restores gut barrier integrity and then ameliorates colitis by improving gut microbiota composition and regulating BA metabolism, including increasing hydrophilic BAs. Full article

Soil-borne pathogens cause devastating root rot diseases in forest ecosystems, often by inducing dysbiosis in the rhizosphere microbiome. While antagonistic bacteria can suppress disease, their effects frequently extend beyond direct inhibition to include ecological restructuring of resident microbial communities. However, the causal relationships between such microbiome restructuring and disease suppression in tree species remain poorly understood. Here, we show that the antagonistic bacterium B. mojavensis dxk33 effectively suppresses F. solani-induced root rot in C. lanceolata, and that this disease suppression coincides with a partial reversal of pathogen-associated dysbiosis in the rhizosphere. Inoculation with dxk33 significantly promoted plant growth and reduced the disease index by 72.19%, while concurrently enhancing soil nutrient availability and key C-, N- and P-cycling enzyme activities. High-throughput sequencing revealed that dxk33 inoculation substantially reshaped the rhizosphere microbiome, counteracting the pathogen’s negative impact on microbial diversity and coinciding with a shift toward a more stable community structure. Under pathogen stress, dxk33 enriched beneficial bacterial taxa such as Pseudomonas and Sphingomonas and suppressed pathogenic fungi while promoting beneficial fungi such as Mortierella. Linear discriminant analysis and functional prediction further indicated that dxk33 remodeled ecological guilds enriched for mycorrhizal and saprotrophic fungi, and reactivated bacterial metabolic pathways and signaling networks that were suppressed by the pathogen. Taken together, our findings are consistent with a multi-tiered mode of action in which direct antagonism by B. mojavensis dxk33 operates alongside associated changes in the rhizosphere microbiome that resemble a disease-suppressive state, although the present experimental design does not allow a strictly causal role for microbiome reconfiguration in disease suppression to be established. This study provides a mechanistic framework for understanding how microbiome engineering may mitigate soil-borne diseases in perennial trees and highlights the potential of targeted microbial interventions for sustainable forest management. Full article

Methamphetamine (MA) abuse has emerged as a multisystem insult driving cardiovascular and neurovascular consequences. Methamphetamine-associated cardiomyopathy (MACM) remains an underrecognized cause of cardioembolic stroke through left ventricular thrombus (LVT) formation. MA-induced gut dysbiosis and enteric neural disruption exacerbate systemic inflammation and autonomic imbalance, resulting in broader dysregulation of the brain–heart–gut axis. This study aimed to synthesize contemporary evidence on chronic MA exposure and its role in LVT formation, stroke pathogenesis, diagnostic approaches, and anticoagulation management. We conducted a focused narrative review of PubMed- and Scopus-indexed literature (1990–2025) addressing cardiovascular, neurovascular, and gut-mediated consequences of chronic MA exposure. Observational cohorts and case reports were integrated to characterize pathophysiology, imaging approaches, and therapeutic considerations, supplemented by a representative clinical case. Chronic MA exposure mediates persistent catecholamine excess, myocardial fibrosis, ventricular dysfunction, and a prothrombotic milieu. Gut dysbiosis-related inflammation and autonomic dysregulation further promote intracardiac stasis. Affected individuals are typically young men with severe systolic dysfunction (left ventricular ejection fraction 20–30%), with a substantial proportion demonstrating apical or mural LVT on systematic imaging. Case-level evidence highlights a broader systemic embolic burden, involving the limbs, kidneys, and aorta. Echocardiography remains the first-line screening method, while cardiac CT and MRI offer greater sensitivity for thrombus detection. Anticoagulation is challenged by bleeding risk, inconsistent adherence, and the absence of standardized protocols. MACM represents a critical and underrecognized etiology of cardioembolic stroke in young adults. Early recognition of brain–heart–gut axis disruption, systematic cardiac imaging, and individualized anticoagulation are crucial for preventing emboli. Prospective registries and standardized imaging-guided treatment strategies are needed to improve outcomes in this high-risk population. Full article

The gut microbiome plays a vital role in metabolism and can be significantly influenced by body mass index (BMI). This study investigated the variations in gut microbial composition and function across different BMI categories by analyzing 16S rRNA sequencing data of 126 stool samples. While our analysis of microbial diversity did not reveal significant differences among BMI groups, a differential abundance analysis identified specific bacterial genera associated with BMI status. Notably, Lachnospira, Lactobacillus, and Roseburia were enriched in non-obese individuals, while Phascolarctobacterium showed greater abundance in obese subjects. Functional profiling utilizing PICRUSt2 and DESeq2 revealed fifteen KEGG pathways that exhibited significant alterations across varying BMI groups. Notably, several of these pathways were associated with short-chain fatty acid (SCFA)-producing taxa, including Lactobacillales and Tannerellaceae. Additionally, covariance network analysis identified the microbial genera Alistipes and Bilophila as central participants in multiple metabolic pathways, particularly those associated with steroid biosynthesis and pathogenic Escherichia coli, which showed a notable enrichment in individuals with obesity. These findings suggest that BMI influences the composition and metabolic potential of the gut microbiome, highlighting the importance of functional profiling to better understand the mechanisms underlying obesity. Full article

Background/Objectives: High-fat diets (HFDs) are widely used to induce obesity, but cost-effective and reproducible formulations remain challenging. Moreover, the reversibility of metabolic and gut microbiota alterations following HFD withdrawal is not fully understood. This study evaluated a low-cost HFD model in mice and investigated metabolic, oxidative, and gut microbiota changes during a subsequent 12-week dietary normalization phase. Methods: Male C57BL/6 mice were fed a standard diet (CTN) or a lard-supplemented HFD for 12 weeks (Phase 1), followed by 12 weeks dietary normalization to a standard diet (Phase 2). Body weight, adiposity, blood glucose, biochemical parameters, and oxidative markers were assessed. Fecal samples were analyzed for short-chain fatty acids (SCFAs), microbiota composition (16S rRNA sequencing), and predicted functions using FAPROTAX and PICRUSt2. Results: The HFD significantly increased body weight, abdominal circumference, the Lee index, and adipose tissue mass compared to CTN. Following diet normalization, both groups exhibited weight loss, but the previously obese mice maintained a higher Lee index and distinct lipid and uric acid profiles. No hepatic oxidative stress was detected after normalization. SCFA profiles underwent a temporal shift: CTN showed higher fecal acetate, while HFD mice exhibited elevated butyrate. Functional prediction revealed one pathway associated with an unclassified Rickettsiales bacterium that was exclusively found in HFD mice. The CTN group exhibited a higher abundance of the thiamine diphosphate formation pathway (PWY-7357), suggesting enhanced oxidative metabolism. Conclusions: This low-cost HFD successfully induced obesity and dysbiosis. Dietary normalization resulted in a partial modulation of metabolic and microbial balance, thereby highlighting host–microbe metabolic plasticity. Full article