Effects of sanitary conditions with lipopolysaccharide injection and dietary valine supplementation on growth performance, immune response, bacterial profile, and microbial metabolites in weaned pigs.

This study investigated the effects of dietary L-valine (Val) supplementation and sanitary conditions with lipopolysaccharide injection on growth performance, immune response, and intestinal bacterial profiles and metabolites in weaned pigs. Thirty-two weaned pigs (6.98 ± 0.47 kg) were randomly assigned to treatments in a 2 × 2 factorial arrangement based on dietary Val levels and sanitary conditions (low or high). The pigs were fed either a basal diet containing the standard levels of Val suggested by (NRC), (2012) or a basal diet supplemented with 0.1% L-Val. A room designated as a high sanitary room was washed weekly, whereas the designated low sanitary room was not washed throughout the experiment and 5 kg of manure from the nursery pig barn was spread on the pen floors on day 1. All data were analysed using a mixed procedure of SAS, with the individual pen as the experimental unit. The pigs raised in low sanitary conditions exhibited a lower (p < 0.05) average daily gain, average daily feed intake, and gain-to-feed ratio and a higher (p < 0.05) incidence of diarrhoea than those raised in high sanitary conditions during the 14-d experimental period. The pigs in the low sanitary group also had a lower (p < 0.05) concentration of butyrate in the jejunum and a higher (p < 0.05) concentration of NH3-N in the colon than those in the high sanitary group. Dietary Val supplementation was reduced (p < 0.05) plasma interleukin (IL)-1ß and IL-1 receptor antagonist concentrations as well as isovalerate and NH3-N concentrations in the colon, regardless of sanitary conditions. Interactions between dietary Val supplementation and sanitary conditions were observed in the abundances of mRNA-encoding ß-defensins 113, 125 and 129 (p < 0.05). In conclusion, dietary Val supplementation beneficially modulates inflammatory responses and microbial metabolites regardless of sanitary conditions while transcriptional levels of ß-defensins are regulated by dietary Val supplementation in a manner dependent on housing hygiene conditions.

Study on the role of microbial metabolites in in-situ noncontact bioleaching of ion-adsorption rare earth ore.

Ion adsorption rare earth ore nearly satisfy global market demand for heavy rare earth elements (HREEs). Bio-leaching has important potential for the clean and efficient extraction of ion-adsorption rare earth ore. However, the complexities of in-situ mining restrict the use of contact/direct bio-leaching, and non-contact/indirect bio-leaching would be the best choice. This study explore the potential of fermentation broths prepared by Yarrowia lipolytica (ATCC 30162) for the bio-leaching of ion-adsorption rare earth ore, and three typical metabolites (potassium citrate (K3Cit), sodium citrate (Na3Cit) and ammonium citrate ((NH4)3Cit) of Yarrowia lipolytica were further evaluated in simulated bioleaching (non-contact bioleaching) of ion-adsorption rare earth ore, including leaching behavior, seepage rule and rare earth elements (REEs) morphological transformation. The column leaching experiments shown that direct leaching of REEs using fermentation broths results in incomplete leaching of REEs due to the influence of impurities. Using the purified and prepared metabolites as lixiviant, REEs can be effectively extracted (leaching efficiency >90%) at cation concentration was only 10 % of the commonly used ammonium sulfate concentration (45 mM). Cation type had less effect on leaching efficiency. During the ion-adsorption rare earth ore leaching process, rare earth ions form a variety of complex chelates with citrate, thus transferring rare earth elements from the mineral surface to the leachate. Experimental results showed that pH and concentration together determined the type and form of rare earth chelates, which in turn affect the leaching behavior of REEs and solution seepage rule. This study helps to provide a theoretical basis for the regulation and enhancement of ion-adsorption rare earth ore non-contact bioleaching process.

Characteristics of stachyose-induced effects on gut microbiota and microbial metabolites in vitro associated with obesity in children.

Childhood obesity presents a serious health concern associated with gut microbiota alterations. Dietary interventions targeting the gut microbiota have emerged as promising strategies for managing obesity in children. This study aimed to elucidate the impact of stachyose (STS) supplementation on the gut microbiota composition and metabolic processes in obese children. Fecal samples were collected from 40 obese children (20 boys and 20 girls) aged between 6 and 15 and in vitro fermentation was conducted with or without the addition of STS, respectively, followed by 16S rRNA amplicon sequencing and analysis of short-chain fatty acids (SCFAs) and gases. Notably, our results revealed that STS supplementation led to significant alterations in gut microbiota composition, including an increase in the abundance of beneficial bacteria such as Bifidobacterium and Faecalibacterium, and a decrease in harmful bacteria including Escherichia-Shigella, Parabacteroides, Eggerthella, and Flavonifractor. Moreover, STS supplementation resulted in changes in SCFAs production, with significant increases in acetate levels and reductions in propionate and propionate, while simultaneously reducing the generation of gases such as H2S, H2, and NH3. The Area Under the Curve (AUC)-Random Forest algorithm and PICRUSt 2 were employed to identify valuable biomarkers and predict associations between the gut microbiota, metabolites, and metabolic pathways. The results not only contribute to the elucidation of STS's modulatory effects on gut microbiota but also underscore its potential in shaping metabolic activities within the gastrointestinal environment. Furthermore, our study underscores the significance of personalized nutrition interventions, particularly utilizing STS supplementation, in the management of childhood obesity through targeted modulation of gut microbial ecology and metabolic function.

Targeting gut-microbiota for gastric cancer treatment: a systematic review.

Background: Preclinical research has identified the mechanisms via which bacteria influence cancer treatment outcomes. Clinical studies have demonstrated the potential to modify the microbiome in cancer treatment. Herein, we systematically analyze how gut microorganisms interact with chemotherapy and immune checkpoint inhibitors, specifically focusing on how gut bacteria affect the pharmacokinetics and pharmacodynamics of cancer treatment. Method: This study searched Web of Science, Scopus, and PubMed until August 2023. Studies were screened by their title and abstract using the Rayyan intelligent tool for systematic reviews. Quality assessment of studies was done using the JBI critical appraisal tool. Result: Alterations in the gut microbiome are associated with gastric cancer and precancerous lesions. These alterations include reduced microbial alpha diversity, increased bacterial overgrowth, and decreased richness and evenness of gastric bacteria. Helicobacter pylori infection is associated with reduced richness and evenness of gastric bacteria, while eradication only partially restores microbial diversity. The gut microbiome also affects the response to cancer treatments, with higher abundances of Lactobacillus associated with better response to anti-PD-1/PD-L1 immunotherapy and more prolonged progression-free survival. Antibiotic-induced gut microbiota dysbiosis can reduce the anti-tumor efficacy of 5-Fluorouracil treatment, while probiotics did not significantly enhance it. A probiotic combination containing Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus can reduce inflammation, enhance immunity, and restore a healthier gut microbial balance in gastric cancer patients after partial gastrectomy. Conclusion: Probiotics and targeted interventions to modulate the gut microbiome have shown promising results in cancer prevention and treatment efficacy.Systematic review registration: https://osf.io/6vcjp.

Exploring gut microbial metabolites as key players in inhibition of cancer progression: Mechanisms and therapeutic implications.

The gut microbiota plays a critical role in numerous biochemical processes essential for human health, such as metabolic regulation and immune system modulation. An increasing number of research suggests a strong association between the gut microbiota and carcinogenesis. The diverse metabolites produced by gut microbiota can modulate cellular gene expression, cell cycle dynamics, apoptosis, and immune system functions, thereby exerting a profound influence on cancer development and progression. A healthy gut microbiota promotes substance metabolism, stimulates immune responses, and thereby maintains the long-term homeostasis of the intestinal microenvironment. When the gut microbiota becomes imbalanced and disrupts the homeostasis of the intestinal microenvironment, the risk of various diseases increases. This review aims to elucidate the impact of gut microbial metabolites on cancer initiation and progression, focusing on short-chain fatty acids (SCFAs), polyamines (PAs), hydrogen sulfide (H2S), secondary bile acids (SBAs), and microbial tryptophan catabolites (MTCs). By detailing the roles and molecular mechanisms of these metabolites in cancer pathogenesis and therapy, this article sheds light on dual effects on the host at different concentrations of metabolites and offers new insights into cancer research.

The central role of the gut microbiota in the pathophysiology and management of type 2 diabetes.

The inhabitants of our intestines, collectively called the gut microbiome, comprise fungi, viruses, and bacterial strains. These microorganisms are involved in the fermentation of dietary compounds and the regulation of our adaptive and innate immune systems. Less known is the reciprocal interaction between the gut microbiota and type 2 diabetes mellitus (T2DM), as well as their role in modifying therapies to reduce associated morbidity and mortality. In this review, we aim to discuss the existing literature on gut microbial strains and their diet-derived metabolites involved in T2DM. We also explore the potential diagnostics and therapeutic avenues the gut microbiota presents for targeted T2DM management. Personalized treatment plans, driven by diet and medication based on the patient's microbiome and clinical markers, could optimize therapy.

Microbial Metabolites-Induced Epigenetic Modifications for Inhibition of Colorectal Cancer: Current Status and Future Perspectives.

Globally, one of the most prevalent cancers is colorectal cancer (CRC). Chemotherapy and surgery are two common conventional CRC therapies that are frequently ineffective and have serious adverse effects. Thus, there is a need for complementary and different therapeutic approaches. The use of microbial metabolites to trigger epigenetic alterations as a way of preventing CRC is one newly emerging field of inquiry. Small chemicals called microbial metabolites, which are made by microbes and capable of altering host cell behaviour, are created. Recent research has demonstrated that these metabolites can lead to epigenetic modifications such as histone modifications, DNA methylation, and non-coding RNA regulation, which can control gene expression and affect cellular behaviour. This review highlights the current knowledge on the epigenetic modification for cancer treatment, immunomodulatory and anti-carcinogenic attributes of microbial metabolites, gut epigenetic targeting system, and the role of dietary fibre and gut microbiota in cancer treatment. It also focuses on short-chain fatty acids, especially butyrates (which are generated by microbes), and their cancer treatment perspective, challenges, and limitations, as well as state-of-the-art research on microbial metabolites-induced epigenetic changes for CRC inhibition. In conclusion, the present work highlights the potential of microbial metabolites-induced epigenetic modifications as a novel therapeutic strategy for CRC suppression and guides future research directions in this dynamic field.

Non-SCFA microbial metabolites associated with fiber fermentation and host health.

Dietary fiber is degraded by commensal gut microbes to yield host-beneficial short-chain fatty acids (SCFAs), but personalized responses to fiber supplementation highlight a role for other microbial metabolites in shaping host health. In this review we summarize recent findings from dietary fiber intervention studies describing health impacts attributed to microbial metabolites other than SCFAs, particularly secondary bile acids (2°BAs), aromatic amino acid derivatives, neurotransmitters, and B vitamins. We also discuss shifts in microbial metabolism occurring through altered maternal dietary fiber intake and agricultural practices, which warrant further investigation. To optimize the health benefits of dietary fibers, it is essential to survey a range of metabolites and adapt recommendations on a personalized basis, according to the different functional aspects of the microbiome.

Oleanolic acid alleviating ischemia-reperfusion injury in rat severe steatotic liver via KEAP1/NRF2/ARE.

Severe steatosis in donor livers is contraindicated for transplantation due to the high risk of ischemia-reperfusion injury (IRI). Although Ho-1 gene-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) can mitigate IRI, the role of gut microbiota and metabolites in this protection remains unclear. This study aimed to explore how gut microbiota and metabolites contribute to HO-1/BMMSCs-mediated protection against IRI in severe steatotic livers. Using rat models and cellular models (IAR20 and THLE-2 cells) of steatotic liver IRI, this study revealed that ischemia-reperfusion led to significant liver and intestinal damage, heightened immune responses, impaired liver function, and altered gut microbiota and metabolite profiles in rats with severe steatosis, which were partially reversed by HO-1/BMMSCs transplantation. Integrated microbiome and metabolome analyses identified gut microbial metabolite oleanolic acid as a potential protective agent against IRI. Experimental validation showed that oleanolic acid administration alone alleviated IRI and inhibited ferroptosis in both rat and cellular models. Network pharmacology and molecular docking implicated KEAP1/NRF2 pathway as a potential target of oleanolic acid. Indeed, OA experimentally upregulated NRF2 activity, which underlies its inhibition of ferroptosis and protection against IRI. The gut microbial metabolite OA protects against IRI in severe steatotic liver by promoting NRF2 expression and activity, thereby inhibiting ferroptosis.

The Human Microbiome as a Therapeutic Target for Metabolic Diseases.

The human microbiome functions as a separate organ in a symbiotic relationship with the host. Disruption of this host-microbe symbiosis can lead to serious health problems. Modifications to the composition and function of the microbiome have been linked to changes in host metabolic outcomes. Industrial lifestyles with high consumption of processed foods, alcoholic beverages and antibiotic use have significantly altered the gut microbiome in unfavorable ways. Therefore, understanding the causal relationship between the human microbiome and host metabolism will provide important insights into how we can better intervene in metabolic health. In this review, I will discuss the potential use of the human microbiome as a therapeutic target to improve host metabolism.

Gut microbial metabolites in cancer therapy.

The gut microbiota plays a crucial role in maintaining homeostasis and promoting health. A growing number of studies have indicated that gut microbiota can affect cancer development, prognosis, and treatment through their metabolites. By remodeling the tumor microenvironment and regulating tumor immunity, gut microbial metabolites significantly influence the efficacy of anticancer therapies, including chemo-, radio-, and immunotherapy. Several novel therapies that target gut microbial metabolites have shown great promise in cancer models. In this review, we summarize the current research status of gut microbial metabolites in cancer, aiming to provide new directions for future tumor therapy.

Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity.

Background: The intestinal microbiota can regulate numerous host functions, including the immune response. Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have a major impact on cancer. Specific gut microbial composition and metabolites are associated with tumor status in the host. However, their effects on the antitumor response have scarcely been investigated. Natural killer (NK) cells play an important role in antitumor immunity due to their ability to directly identify and eliminate tumor cells. Methods: The aim of this study was to investigate the effects of SCFAs on antitumoral NK cell activity, using NK-92 cell line. Results: Here, we describe how SCFAs can boost antitumoral NK cell activity. The SCFAs induced the release of NK extracellular vesicles and reduced the secretion of the anti-inflammatory cytokine IL-10. The SCFAs also increased the cytotoxicity of the NK cells against multiple myeloma cells. Conclusions: Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs' production could play a fundamental role in cancer immunotherapy.

Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis.

Metabolic derivatives of numerous microorganisms inhabiting the human gut can participate in regulating physiological activities and immune status of the lungs through the gut-lung axis. The current well-established microbial metabolites include short-chain fatty acids (SCFAs), tryptophan and its derivatives, polyamines (PAs), secondary bile acids (SBAs), etc. As the study continues to deepen, the critical function of microbial metabolites in the occurrence and treatment of lung cancer has gradually been revealed. Microbial derivates can enter the circulation system to modulate the immune microenvironment of lung cancer. Mechanistically, oncometabolites damage host DNA and promote the occurrence of lung cancer, while tumor-suppresive metabolites directly affect the immune system to combat the malignant properties of cancer cells and even show considerable application potential in improving the efficacy of lung cancer immunotherapy. Considering the crosstalk along the gut-lung axis, in-depth exploration of microbial metabolites in patients' feces or serum will provide novel guidance for lung cancer diagnosis and treatment selection strategies. In addition, targeted therapeutics on microbial metabolites are expected to overcome the bottleneck of lung cancer immunotherapy and alleviate adverse reactions, including fecal microbiota transplantation, microecological preparations, metabolite synthesis and drugs targeting metabolic pathways. In summary, this review provides novel insights and explanations on the intricate interplay between gut microbial metabolites and lung cancer development, and immunotherapy through the lens of the gut-lung axis, which further confirms the possible translational potential of the microbiome metabolome in lung cancer treatment.

Gubra Amylin-NASH Diet Induced Nonalcoholic Fatty Liver Disease Associated with Histological Damage, Oxidative Stress, Immune Disorders, Gut Microbiota, and Its Metabolic Dysbiosis in Colon.

SCOPE: The overall changes of colon under nonalcoholic fatty liver disease (NAFLD) remain to be further elucidated. METHODS AND RESULTS: This study establishes a mouse model of NAFLD through a long-term Gubra Amylin-nonalcoholic steatohepatitis (NASH) diet (GAN diet). The results show that GAN diet significantly induces weight gain, liver steatosis, colonic oxidative stress, and lipid accumulation in blood, liver, and adipose tissue in mice. GAN feeding reduces the diversity of the gut microbiota, alters the composition and abundance of the gut microbiota, and leads to an increase in microbial metabolites such as long-chain fatty acids (LCFAs) and secondary bile acids (BAs), as well as a decrease in short-chain fatty acids (SCFAs). The RNA-seq and immunofluorescence results reveal that the GAN diet alters the expression of proteins and their coding genes involved in oxidative stress, immune response, and barrier function in colon tissue, such as lipocalin-2 (Lcn2, p < 0.05), heme oxygenase-1 (HO-1/Hmox1, p < 0.05), interferon-gamma (IFN-γ), and claudin-3/7. In addition, correlation analysis indicates a strong correlation between the changes in gut microbiota and lipid biomarkers. Additionally, the expression of immune related genes in colon tissue is related to the LCFAs produced by microbial metabolism. CONCLUSION: GAN-induced NAFLD is related to microbiota and its metabolic imbalance, oxidative stress, immune disorders, and impaired barrier function in colon.

Synergistic impacts of antibiotics and heavy metals on Hermetia illucens: Unveiling dynamics in larval gut bacterial communities and microbial metabolites.

Hermetia illucens larvae showcases remarkable bioremediation capabilities for both antibiotics and heavy metal contaminants. However, the distinctions in larval intestinal microbiota arising from the single and combined effects of antibiotics and heavy metals remain poorly elucidated. In this study, we delved into the details of larval intestinal bacterial communities and microbial metabolites when exposed to single and combined contaminants of oxytetracycline (OTC) and hexavalent chromium (Cr(VI)). After conversion, single contaminant-spiked substrate showed 75.5% of OTC degradation and 95.2% of Cr(VI) reductiuon, while combined contaminant-spiked substrate exhibited 71.3% of OTC degradation and 93.4% of Cr(VI) reductiuon. Single and combined effects led to differences in intestinal bacterial communities, mainly reflected in the genera of Enterococcus, Pseudogracilibacillus, Gracilibacillus, Wohlfahrtiimonas, Sporosarcina, Lysinibacillus, and Myroide. Moreover, these effects also induced differences across various categories of microbial metabolites, which categorized into amino acid and its metabolites, benzene and substituted derivatives, carbohydrates and its metabolites, heterocyclic compounds, hormones and hormone-related compounds, nucleotide and its metabolites, and organic acid and its derivatives. In particular, the differences induced OTC was greater than that of Cr(VI), and combined effects increased the complexity of microbial metabolism compared to that of single contaminant. Correlation analysis indicated that the bacterial genera, Preudogracilibacillus, Enterococcus, Sporosarcina, Lysinibacillus, Wohlfahrtiimonas, Ignatzschineria, and Fusobacterium exhibited significant correlation with significant differential metabolites, these might be used as indicators for the resistance and bioremediation of OTC and Cr(VI) contaminants. These findings are conducive to further understanding that the metabolism of intestinal microbiota determines the resistance of Hermetia illucens to antibiotics and heavy metals.

Biomolecule-Producing Probiotic Bacterium Lactococcus lactis in Free or Nanoencapsulated Form for Endometritis Treatment and Fertility Improvement in Buffaloes.

A Lactococcus (L.) lactis strain producing antimicrobial and anti-inflammatory biomolecules (mainly 1,4-Diaza-2,5-dioxobicyclo[4.3.0]nonanes and pyrazine-derivatives) was tested for its capacity to cure clinical endometritis in buffaloes compared to conventional antibiotic-based treatment. Clinical endometritis-diagnosed buffaloes (n = 16/group) were infused intrauterine with four doses of 109 CFU-free (FLC group) or nanoencapsulated L. lactis (NLC group) and compared to those that received three doses of saline + a single dose of 500 mg cephapirin benzathin (AB group) or four doses of saline (control, C group) every other day. Endometrium samples were analyzed for cytological (polymorphonuclear cells, PMN), bacteriological, and proinflammatory mRNA expression. Uterine wash and blood samples were collected to determine proinflammatory cytokine concentrations and metabolites in the blood samples. The reproductive performance of buffaloes was assessed. Compared to the C group, the AB and NLC groups had the lowest percentage of PMN, followed by those in the FLC group (p < 0.05). All treated buffaloes had significantly lower numbers of pathogens than the control buffaloes. Compared to control, all treatments significantly down-regulated endometrial proinflammatory encoding mRNA expression. The concentrations of IL1B, TNFAIP7, and leukocyte esterase activity in the uterine washings were significantly decreased in the AB and NLC groups compared to the C and FLC groups. All treatments significantly decreased concentrations of serum proinflammatory cytokines compared to control. Both the AB and NLC groups had significantly lower concentrations of serum NEFA than the C and FLC groups. The percentage of control buffaloes having an echogenic uterus and PVD score > 2 was significantly higher than those in the treated buffaloes with higher numbers of corpora lutea, higher conception rates, and shorter days open than control buffaloes (p < 0.05). In conclusion, L. lactis-producing antimicrobial and anti-inflammatory metabolites reduce uterine inflammatory responses and improve fertility in buffaloes.

Microbial metabolites affect tumor progression, immunity and therapy prediction by reshaping the tumor microenvironment (Review).

Several studies have indicated that the gut microbiome and tumor microbiota may affect tumors. Emerging metabolomics research illustrates the need to examine the variations in microbial metabolite composition between patients with cancer and healthy individuals. Microbial metabolites can impact the progression of tumors and the immune response by influencing a number of mechanisms, including modulation of the immune system, cancer or immune­related signaling pathways, epigenetic modification of proteins and DNA damage. Microbial metabolites can also alleviate side effects and drug resistance during chemotherapy and immunotherapy, while effectively activating the immune system to exert tumor immunotherapy. Nevertheless, the impact of microbial metabolites on tumor immunity can be both beneficial and harmful, potentially influenced by the concentration of the metabolites or the specific cancer type. The present review summarizes the roles of various microbial metabolites in different solid tumors, alongside their influence on tumor immunity and treatment. Additionally, clinical trials evaluating the therapeutic effects of microbial metabolites or related microbes on patients with cancer have been listed. In summary, studying microbial metabolites, which play a crucial role in the interaction between the microbiota and tumors, could lead to the identification of new supplementary treatments for cancer. This has the potential to improve the effectiveness of cancer treatment and enhance patient prognosis.

Microbiome Dysbiosis, Dietary Intake and Lifestyle-Associated Factors Involve in Epigenetic Modulations in Colorectal Cancer: A Narrative Review.

Background: Colorectal cancer is the second cause of cancer mortality and the third most commonly diagnosed cancer worldwide. Current data available implicate epigenetic modulations in colorectal cancer development. The health of the large bowel is impacted by gut microbiome dysbiosis, which may lead to colon and rectum cancers. The release of microbial metabolites and toxins by these microbiotas has been shown to activate epigenetic processes leading to colorectal cancer development. Increased consumption of a 'Westernized diet' and certain lifestyle factors such as excessive consumption of alcohol have been associated with colorectal cancer.Purpose: In this review, we seek to examine current knowledge on the involvement of gut microbiota, dietary factors, and alcohol consumption in colorectal cancer development through epigenetic modulations.Methods: A review of several published articles focusing on the mechanism of how changes in the gut microbiome, diet, and excessive alcohol consumption contribute to colorectal cancer development and the potential of using these factors as biomarkers for colorectal cancer diagnosis.Conclusions: This review presents scientific findings that provide a hopeful future for manipulating gut microbiome, diet, and alcohol consumption in colorectal cancer patients' management and care.

Untargeted metabolomics unravels distinct gut microbial metabolites derived from plant-based and animal-origin proteins using in vitro modeling.

The popularity of plant-based meat alternatives (PBMAs) has sparked a contentious debate about their influence on intestinal homeostasis compared to traditional animal-based meats. This study aims to explore the changes in gut microbial metabolites (GMMs) induced by the gut microbiota on different digested patties: beef meat and pea-protein PBMA. After digesting in vitro, untargeted metabolomics revealed 32 annotated metabolites, such as carnitine and acylcarnitines correlated with beef meat, and 45 annotated metabolites, like triterpenoids and lignans, linked to our PBMA. Secondly, (un)targeted approaches highlighted differences in GMM patterns during colonic fermentations. Our findings underscore significant differences in amino acids and their derivatives. Beef protein fermentation resulted in higher production of methyl-histidine, gamma-glutamyl amino acids, indoles, isobutyric and isovaleric acids. In contrast, PBMAs exhibit a significant release of N-acyl amino acids and unique dipeptides, like phenylalanine-arginine. This research offers valuable insights into how PBMAs and animal-based proteins differently modulate intestinal microenvironments.