Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

Understanding global temporal and spatial variations in breast milk composition is crucial for developing personalized infant nutrition strategies. This study analyzed 46,673 breast milk samples from 171 studies using a random-effects model to evaluate total fatty acids (TFA), sn-2 fatty acids (sn-2 FA), and triacylglycerols (TAG) across lactation stages, regions, and sample years. Results showed that saturated fatty acids (SFA) increased while unsaturated fatty acids (UFA) decreased with prolonged lactation, with corresponding changes in triacylglycerol profiles. Geographically, Africa had the highest SFA and lowest UFA, Asia had the highest PUFA, and Europe had the highest MUFA. Over time, SFA and SFA-dominant TAGs declined, while UFA and UFA-dominant TAGs rose. These variations reflect shifts in maternal diet, infant nutritional needs, and potential growth outcomes, highlighting the importance of monitoring breast milk lipids to optimize infant nutrition strategies.

Breast cancer occurs at a younger age compared to western countries in South Korea. Despite advancements in treatment methods such as targeted therapy and immunotherapy, the increasing number of patients underscores the importance of improving disease-free survival (DFS). In this study, we evaluated the associations between gut microbiota composition, inflammatory cytokine levels, and breast cancer recurrence in preoperative patients. Additionally, we developed a composite prognostic index by integrating these factors with PET/CT indices and clinical prognostic factors. This study showed that Prevotella abundance was significantly higher in the DFS group than in the recurrence group, and higher Prevotella abundance was associated with lower levels of the inflammatory cytokine IL-1β. Survival analysis revealed that patients with low Prevotella abundance and high IL-1β levels had a higher risk of breast cancer recurrence. PET markers, such as SUVtumor, SUVVAT, and SUVspleen, were also found to be significant prognostic indicators, with lower values associated with better survival outcomes. An integrated predictive model combining gut microbiota composition, cytokine levels, PET indices, and clinical factors demonstrated superior accuracy (AUC: 0.9025) in predicting breast cancer recurrence compared to individual components.

Coffee is globally popular beverage, renowned for its taste and stimulating properties. This study aims to explore the impact of two different types of coffee, depending on extraction methods, on the gut microbiota. Fecal samples from healthy donors (n = 20) were cultured with or without coffee using in vitro fecal incubation. Both coffee-treated groups exhibited lower microbial diversity and greater structural differences in their communities compared to the control. Notably, the Bifidobacterium genus was overrepresented in the instant coffee (IC)-treated groups, whereas the Blautia genus was underrepresented in both coffee-treated groups. Additionally, genes for TCA cycle and vitamin B6 metabolism were more prevalent in coffee-treated groups than in the control. However, the precursor pathways leading to the TCA cycle differed between the DC- and IC-treated groups, reflecting the distinct chemical compositions of each coffee type. These findings demonstrate that extraction method of coffee significantly affects its impacts on gut microbial structure.

The online version contains supplementary material available at 10.1007/s10068-024-01717-7.

Colorectal cancer has the second highest mortality among cancer sites worldwide, with increasing morbidity, high recurrence rates, and even poorer postoperative quality of life. Therefore, preventive strategies for colorectal cancer should be established. This study aimed to cross-sectionally explore dietary patterns affecting the intestinal metabolism of bile acids (BAs), a risk factor for colorectal cancer, in young Japanese women. We collected fecal samples for intestinal microbiota and BA analysis. We used the Bristol scale to determine 1-week defecation status. Moreover, the brief-type self-administered diet history questionnaire was used for habitual dietary intake status. Reduced-rank regression analysis revealed dietary patterns related to fecal BA levels. The relationship between dietary patterns and fecal BA levels was adjusted for defecation status and intestinal microbiota variables using analysis of covariance. Reduced-rank regression analysis generated two dietary pattern scores related to fecal BA levels. First, the score was associated with a greater intake of leafy and root vegetables, and higher values were associated with greater fecal cholic and chenodeoxycholic acid levels and lower deoxycholic and lithocholic acid levels. Second, the score was associated with greater rice intake and lower Western sweets, pork, beef, and egg intake, and higher values were associated with lower deoxycholic and lithocholic acid levels. These relationships remained after adjusting for intestinal microbiota and defecation status variables.

Taurine, although not a coding amino acid, is the most common free amino acid in the body. Taurine has multiple and complex functions in protecting mitochondria against oxidative-nitrosative stress. In this comprehensive review paper, we introduce a novel potential role for taurine in protecting from deuterium (heavy hydrogen) toxicity. This can be of crucial impact to either normal or cancer cells that have highly different mitochondrial redox status. Deuterium is an isotope of hydrogen with a neutron as well as a proton, making it about twice as heavy as hydrogen. We first explain the important role that the gut microbiome and the gut sulfomucin barrier play in deuterium management. We describe the synergistic effects of taurine in the gut to protect against the deleterious accumulation of deuterium in the mitochondria, which disrupts ATP synthesis by ATPase pumps. Moreover, taurine's derivatives, N-chlorotaurine (NCT) and N-bromotaurine (NBrT), produced through spontaneous reaction of taurine with hypochlorite and hypobromite, have fascinating regulatory roles to protect from oxidative stress and beyond. We describe how taurine could potentially alleviate deuterium stress, primarily through metabolic collaboration among various gut microflora to produce deuterium depleted nutrients and deuterium depleted water, and in this way protect against leaky gut barrier, inflammatory bowel disease, and colon cancer.

The probiotic gut microbiome and its metabolites are pivotal in regulating host metabolism, inflammation, and immunity. Host genetics, colonization at birth, the host lifestyle, and exposure to diseases and drugs determine microbial composition. Dysbiosis and disruption of homeostasis in the beneficial microbiome have been reported to be involved in the tumorigenesis and progression of colorectal cancer (CRC). However, the influence of bacteria-secreted metabolites on CRC growth is yet to be fully elucidated. In this study, we compared the microbial composition of CRC patients to healthy controls to identify distinct patterns of microbiota-derived metabolites in CRC patients. Metagenomic analysis demonstrated that beneficial bacteria strains; Blautia producta, Bifidobacterium adolescentis, and Bifidobacterium longum decreased, while Parabacteroides distasonis and Bacteroides ovatus were more prevalent in the CRC patient group. Treatment of cancer organoid lines with microbial culture supernatants from Blautia producta, Bifidobacterium adolescentis, and Bifidobacterium longum showed remarkable inhibition of cancer growth. This study demonstrates that the bacterial metabolites depleted in CRC patients may inhibit cancer growth and highlights the effects of microbiome-derived metabolites on CRC growth.

Recent studies suggest the role of gut microbes in bile acid metabolism in the development and progression of colorectal cancer. However, the surveys of the association between fecal bile acid concentrations and colorectal cancer (CRC) have been inconsistent. We searched online to identify relevant cross-sectional and case-control studies published online in the major English language databases (Medline, Embase, Web of Science, AMED, and CINAHL) up to January 1, 2024. We selected studies according to inclusion and exclusion criteria and extracted data from them. RevMan 5.3 was used to perform the meta-analyses. In CRC risk meta-analysis, the effect size of CA (cholic acid), CDCA (chenodeoxycholic acid), DCA (deoxycholic acid), and UDCA (ursodeoxycholic acid) were significantly higher (CA: standardized mean difference [SMD] = 0.41, 95% confidence interval [CI]: 0.5-0.76, P = 0.02; CDCA: SMD = 0.35, 95% CI: 0.09-0.62, P = 0.009; DCA: SMD = 0.33,95% CI: 0.03-0.64, P = 0.03; UDCA: SMD = 0.46, 95% CI: 0.14-0.78, P = 0.005), and the combined effect size was significantly higher in the high-risk than the low-risk CRC group (SMD = 0.36, 95% CI: 0.21-0.51, P < 0.00001). In the CRC incidence meta-analysis, the effect sizes of CA and CDCA were significantly higher (CA: SMD = 0.42, 95% CI: 0.04-0.80, P = 0.03; CDCA: SMD = 0.61, 95% CI: 0.26-0.96, P = 0.00079), and their combined effect size was also significantly higher in the high-risk compared to low-risk CRC group (SMD = 0.39, 95% CI: 0.09-0.68, P = 0.01). Only one cross-sectional study suggested a higher concentration of CDCA, DCA, and UDCA in the stool of the CRC high-risk group than the low-risk group. These findings indicate that higher fecal concentrations of bile acid may be associated with a higher risk/incidence of CRC.

The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood-brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.

Obesity is associated with structural deterioration in the gut. Yoyo dieting, which refers to repeated phases of dieting and non-dieting periods leading to cyclic weight loss and regain, is a common occurrence in individuals with obesity. However, there is limited evidence on how gut structures are affected in yoyo dieting. There is good evidence suggesting that increased intake of resistant starch (RS) may be beneficial in promoting structural improvements in the gut. This investigation aimed to explore the effect of yoyo dieting on gastrointestinal structure and whether RS has beneficial effects in improving obesity-related gastrointestinal damage.

In this study, male and female C57BL/6 mice were assigned to six different diets for 20 weeks: (1) control diet, (2) high fat diet (HF), (3) yoyo diet (alternating HF and control diets every 5 weeks), (4) control diet with RS, (5) HF with RS, and (6) yoyo diet with RS. Distal colon was collected for epithelial barrier integrity measurement. The small and large intestines were collected for histological assessment.

After 20 weeks, yoyo dieting resulted in increased colonic inflammation and exacerbated mucosal damage in comparison with continuous HF diet feeding. RS supplemented in HF and yoyo diets reduced mucosal damage in comparison to diets without RS. However, RS supplementation in a control diet significantly increased inflammation, crypt length, and goblet cell density. There were no significant differences in epithelial change and epithelial barrier integrity across diet groups.

This study suggests that yoyo dieting worsens gut damage, and incorporating high levels of RS may be detrimental in the absence of dietary challenge.

Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.

This is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50 g/day from whole foods) or healthy control diet (target fiber 20 g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.

This DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.

This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.

International migration often results in major changes in living environments and lifestyles, and these changes may lead to the observed increases in obesity and diabetes among foreign-born people after resettling in higher-income countries. A possible mechanism linking changes in living environments to the onset of health conditions may be changes in the microbiome. Previous research has shown that unfavorable changes in the composition of the microbiome can increase disposition to diseases such as diabetes, obesity, kidney disease, and inflammatory bowel disease. We investigated the relationship between human migration and microbiome composition through a review using microbiome- and migration-related search terms in PubMed and Web of Science. We included articles examining the gut, oral, or oropharyngeal microbiome in people who migrated internationally. Nine articles met eligibility criteria. All but one examined migration from a non-Western to a Western country. Four of these found a difference in the microbiome of migrants compared with non-migrating residents of their country of birth, seven found differences in the microbiome of migrants compared with the native-born population in the country of resettlement, and five found microbiome differences associated with duration of stay in the country of resettlement. Microbiome composition varies with country of birth, age at migration, time since immigration, and country of resettlement. The results suggest that migration may lead to changes in the microbiome; thus, microbiome characteristics are a plausible pathway to examine changes in health after resettlement in a new country.

The gut microbiome plays a crucial role in human health, affecting metabolic, immune, and cognitive functions. While the impact of various dietary components on the microbiome is well-studied, the effect of legumes remains less explored. This review examines the influence of legume consumption on gut microbiome composition, diversity, and metabolite production, based on 10 human and 21 animal studies. Human studies showed mixed results, with some showing increased microbial diversity and others finding no significant changes. However, legume consumption was linked to increases in beneficial bacteria like Bifidobacterium and Faecalibacterium. Animal studies generally indicated enhanced microbial diversity and composition changes, though these varied by legume type and the host's health. Some studies highlighted legume-induced shifts in bacteria associated with better metabolic health. Overall, the review emphasizes the complexity of legume-microbiome interactions and the need for standardized methodologies and longitudinal studies. While legumes have the potential to positively affect the gut microbiome, the effects are nuanced and depend on context. Future research should investigate the long-term impacts of legume consumption on microbiome stability and its broader health implications, particularly for disease prevention and dietary strategies.

An imbalance between primary and secondary bile acids contributes to the development of metabolic dysfunction-associated steatohepatitis (MASH). The precise mechanisms underlying changes in the bile acid pool in MASH remain to be identified. As gut bacteria convert primary bile acids to secondary bile acids, we investigated the contribution of the gut microbiota and its metabolizing activities to bile acid alterations in MASH.

To disentangle the influence of MASH from environmental and dietary factors, high-fat diet fed foz/foz mice were compared with their high-fat diet fed wildtype littermates. We developed functional assays (stable isotope labeling and in vitro experiments) to extend the analyses beyond a mere study of gut microbiota composition (16S rRNA gene sequencing). Key findings were confirmed in C57BL/6J mice were fed a Western and high-fructose diet, as an independent mouse model of MASH.

Although mice with MASH exhibited lower levels of secondary 7α-dehydroxylated bile acids (3.5-fold lower, p = 0.0008), the gut microbial composition was similar in mice with and without MASH. Similar gut microbial bile salt hydrolase and 7α-dehydroxylating activities could not explain the low levels of secondary 7α-dehydroxylated bile acids. Furthermore, the 7α-dehydroxylating activity was unaffected by Clostridium scindens administration in mice with a non-standardized gut microbiota. By exploring alternative mechanisms, we identified an increased bile acid 7α-rehydroxylation mediated by liver CYP2A12 and CYP2A22 enzymes (4.0-fold higher, p <0.0001), that reduces secondary 7α-dehydroxylated bile acid levels in MASH.

This study reveals a gut microbiota-independent mechanism that alters the level of secondary bile acids and contributes to the development of MASH in mice.

Although changes in bile acid levels are implicated in the development of metabolic dysfunction-associated steatohepatitis (MASH), the precise mechanisms underpinning these alterations remain elusive. In this study, we investigated the mechanisms responsible for the changes in bile acid levels in mouse models of MASH. Our results support that neither the composition nor the metabolic activity of the gut microbiota can account for the alterations in the bile acid pool. Instead, we identified hepatic 7α-rehydroxylation of secondary bile acids as a gut microbiota-independent factor contributing to the reduced levels of secondary bile acids in mice with MASH. Further investigation is warranted to understand bile acid metabolism and its physiological implications in clinical MASH. Nonetheless, our findings hold promise for exploring novel therapeutic interventions for MASH.

Short-chain fatty acids (SCFAs) are microbial metabolites in the gut that may play a role in cancer prevention and treatment. They affect the metabolism of both normal and cancer cells, regulating various cellular energetic processes. SCFAs also inhibit histone deacetylases, which are targets for cancer therapy. The three main SCFAs are acetate, propionate, and butyrate, which are transported into cells through specific transporters. SCFAs may enhance the efficacy of chemotherapeutic agents and modulate immune cell metabolism, potentially reprogramming the tumor microenvironment. Although SCFAs and SCFA-generating microbes enhance therapeutic efficacy of several forms of cancer therapy, published data also support the opposing viewpoint that SCFAs mitigate the efficacy of some cancer therapies. Therefore, the relationship between SCFAs and cancer is more complex, and this review discusses some of these aspects. Clearly, further research is needed to understand the role of SCFAs, their mechanisms, and applications in cancer prevention and treatment.

Background. In many studies over the past decade, scientists have made a connection between the composition of gut microbiota and human health. A number of publications have shown that gut bacteria are involved in many metabolic and physiological processes of the organism. The composition of the gut microbiome is unique for each person and is formed under the influence of various factors associated with both the individual characteristics of the body and the characteristics of the environment. Different regional characteristics make it necessary for the body to adapt to certain conditions, including temperature fluctuations. Living in areas with low temperatures, such as the Arctic zone, dictates the need for increased energy consumption, which affects the composition of the gut microbiome. Methods. In our study, an extensive questionnaire was conducted among the participants, where many questions were included about the dietary preferences of the study participants, which allowed them us to further divide them into groups according to their diets. Stool samples were collected from participants from 3 groups: Arctic native, Arctic newcomer and the control group. The next step was the isolation of bacterial DNA and sequencing the 16S rRNA gene. The analysis of the results of the diversity of the intestinal microbiota was carried out both with and without taking into account the dietary preferences of the participants. Results. As a result of comparing the intestinal microbiota obtained from residents of the Arctic zone with the gut microbiota of residents of other regions with a milder climate, significant differences are found. These differences may be related to limited food resources and a reduction in the variety of food products characteristic of this Arctic region. t was also found that representatives of the bacterial families Christensenellaceae and Muribaculaceae dominated the control group, both with traditional nutrition and with a dairy-free diet in comparison with the Arctic groups. The control group was dominated by representatives of the Prevotellaceae, Enterobacteriaceae and Comamonadaceae families compared to the Arctic group (with a traditional diet). The results also show that the number of representatives of the families Desulfovibrionaceae (with traditional diet) and Enterobacteriaceae (with milk-free diet) is growing in the Arctic group. Conclusions. In the course of this work, bacterial families characteristic of people living in the Arc-tic zone of the Far Eastern region of the Russian Federation were identified. Poor diet, difficult climatic conditions, and problems with logistics and medical care can have a strong impact on the health of this population. The main type of diet for the inhabitants of the Arctic is the traditional type of diet. They consume a large number of low-cost products, obtainget animal protein from poultry and canned food, and also eat a small number of fresh vegetables and fruits. Such a diet is due to the social status of the study participants and the climatic and geographical features of the region (difficulties in agriculture). With such a diet, we observe a decrease in representatives of the Christensenellaceae, Muribaculaceae, Eubacteriaceae, and Prevotellaceae families and an increase in representatives of the Enterobacteriaceae and Desulfovibrionaceae families among Arctic residents. This imbalance in the futuremay cause, this population may to develop various diseases in the future, including chronic diseases such as obesity, intestinal dysbiosis, inflammatory bowel diseases, and type 2 diabetes.

The microbiota inhabits the epithelial surfaces of hosts, which influences physiological functions from helping digest food and acquiring nutrition to regulate metabolism and shaping host immunity. With the deep insight into the microbiota, an increasing amount of research reveals that it is also involved in the initiation and progression of cancer. Intriguingly, gut microbiota can mediate the biotransformation of drugs, thereby altering their bioavailability, bioactivity, or toxicity.

The review aims to elaborate on the role of gut microbiota and microbial metabolites in the efficacy and adverse effects of chemotherapeutics. Furthermore, we discuss the clinical potential of various ways to harness gut microbiota for cancer chemotherapy.

Recent evidence shows that gut microbiota modulates the efficacy and toxicity of chemotherapy agents, leading to diverse host responses to chemotherapy. Thereinto, targeting the microbiota to improve efficacy and diminish the toxicity of chemotherapeutic drugs may be a promising strategy in tumor treatment.

Gut microbiota (GM) and metabolic alterations play pivotal roles in lung cancer (LC) development and host genetic variations are known to contribute to LC susceptibility by modulating the GM. However, the causal links among GM, metabolite, host genes, and LC remain to be fully delineated.

Through bidirectional MR analyses, we examined the causal links between GM and LC, and utilized two-step mediation analysis to identify potential mediating blood metabolite. We employed diverse MR methods, including inverse-variance-weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode, to ensure a robust examination of the data. MR-Egger intercept test, Radial MR, MR-PRESSO, Cochran Q test and Leave-one-out (LOO) analysis were used for sensitivity analyses. Analyses were adjusted for smoking, alcohol intake frequency and air pollution. Linkage disequilibrium score regression and Steiger test were used to probe genetic causality. The study also explored the association between specific host genes and the abundance of gut microbes in LC patients.

The presence of Bacteroides clarus was associated with an increased risk of LC (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03-1.11, p = 0.012), whereas the Eubacteriaceae showed a protective effect (OR = 0.82, 95% CI: 0.75-0.89, p = 0.001). These findings remained robust after False Discovery Rate (FDR) correction. Our mediator screening identified 13 blood metabolites that significantly influence LC risk after FDR correction, underscoring cystine and propionylcarnitine in reducing LC risk, while linking specific lipids and hydroxy acids to an increased risk. Our two-step mediation analysis demonstrated that the association between the bacterial pathway of synthesis of guanosine ribonucleotides and LC was mediated by Fructosyllysine, with mediated proportions of 11.38% (p = 0.037). LDSC analysis confirmed the robustness of these associations. Our study unveiled significant host genes ROBO2 may influence the abundance of pathogenic gut microbes in LC patients. Metabolic pathway analysis revealed glutathione metabolism and glutamate metabolism are the pathways most enriched with significant metabolites related to LC.

These findings underscore the importance of GM in the development of LC, with metabolites partly mediating this effect, and provide dietary and lifestyle recommendations for high-risk lung cancer populations.

Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes. We also consider whether those linkages can be disrupted via weight loss therapies, including lifestyle modifications, pharmacotherapy, bariatric surgery, and endobariatrics.

Colorectal cancer is the third most common type of cancer, with a significant burden on healthcare and social systems. Its incidence is constantly rising, due to the spread of unhealthy lifestyle, i.e. Western diet. Increasing evidence suggests that westernization-driven microbiome alterations may play a critical role in colorectal tumorigenesis. The current screening strategies for this neoplasm, mainly fecal immunochemical tests, are burdened by unsatisfactory accuracy. Novel, non-invasive biomarkers are rising as the new frontier of colorectal cancer screening, and the microbiome-based ones are showing positive and optimistic results. This Review describes our current knowledge on the role of gut microbiota in colorectal cancer, from its pathogenetic action to its clinical potential as diagnostic biomarker.

Excess body fat elevates colorectal cancer risk. While bariatric surgery (BRS) induces significant weight loss, its effects on the fecal stream and colon biology are poorly understood. Specifically, limited data exist on the impact of bariatric surgery (BRS) on fecal secondary bile acids (BA), including lithocholic acid (LCA), a putative promotor of colorectal carcinogenesis.

This cross-sectional case-control study included 44 patients with obesity; 15 pre-BRS (controls) vs. 29 at a median of 24.1 months post-BRS. We examined the fecal concentrations of 11 BA by liquid chromatography and gene abundance of BA-metabolizing bacterial enzymes through fecal metagenomic sequencing. Differences were quantified using non-parametric tests for BA levels and linear discriminant analysis (LDA) effect size (LEfSe) for genes encoding BA-metabolizing enzymes.

Total fecal secondary BA concentrations trended towards lower levels post- vs. pre-BRS controls (p = 0.07). Individually, fecal LCA concentrations were significantly lower post- vs. pre-BRS (8477.0 vs. 11,914.0 uM/mg, p < 0.008). Consistent with this finding, fecal bacterial genes encoding BA-metabolizing enzymes, specifically 3-betahydroxycholanate-3-dehydrogenase (EC 1.1.1.391) and 3-alpha-hydroxycholanate dehydrogenase (EC 1.1.1.52), were also lower post- vs. pre-BRS controls (LDA of - 3.32 and - 2.64, respectively, adjusted p < 0.0001). Post-BRS fecal BA concentrations showed significant inverse correlations with weight loss, a healthy diet quality, and increased physical activity.

Concentrations of LCA, a secondary BA, and bacterial genes needed for BA metabolism are lower post-BRS. These changes can impact health and modulate the colorectal cancer cascade. Further research is warranted to examine how surgical alterations and the associated dietary changes impact bile acid metabolism.

Short-chain fatty acids (SCFAs) are essential molecules produced by gut bacteria that fuel intestinal cells and may also influence overall health. An imbalance of SCFAs can result in various acute and chronic diseases, including diabetes, obesity and colorectal cancer (CRC). This review delves into the multifaceted roles of SCFAs, including a brief discussion on their source and various gut-residing bacteria. Primary techniques used for detection of SCFAs, including gas chromatography, high-performance gas chromatography, nuclear magnetic resonance and capillary electrophoresis are also discussed through this article. This review study also compiles various synthesis pathways of SCFAs from diverse substrates such as sugar, acetone, ethanol and amino acids. The different pathways through which SCFAs enter cells for immune response regulation are also highlighted. A major emphasis is the discussion on diseases associated with SCFA dysregulation, such as anaemia, brain development, CRC, depression, obesity and diabetes. This includes exploring the relationship between SCFA levels across ethnicities and their connection with blood pressure and CRC. In conclusion, this review highlights the critical role of SCFAs in maintaining gut health and their implications in various diseases, emphasizing the need for further research on SCFA detection, synthesis and their potential as diagnostic biomarkers. Future studies of SCFAs will pave the way for the development of novel diagnostic tools and therapeutic strategies for optimizing gut health and preventing diseases associated with SCFA dysregulation.

This manuscript provides an overview of the microbiota profile associated with precancerous lesions in the esophagus, stomach, and large bowel. The critical review of the available data reveals significant variability in the methods used for microbiota profiling. This variability may affect the reliable identification of specific biological links between histologically profiled neoplastic diseases and the microbiota population. Overall, this critical review reveals significant links between microbiota communities and the different lesions within the spectrum of the oncogenetic cascade in various epidemiological contexts and anatomical districts.

Emerging evidence reveal that tumor-associated bacteria (TAB) can facilitate the initiation and progression of multiple types of cancer. Recent work has emphasized the significant role of intestinal microbiota, particularly bacteria, plays in affecting responses to chemo- and immuno-therapies. Hence, it seems feasible to improve cancer treatment outcomes by targeting intestinal bacteria. While considering variable richness of the intestinal microbiota and diverse components among individuals, direct manipulating the gut microbiota is complicated in clinic. Tumor initiation and progression requires the gut microbiota-derived metabolites to contact and reprogram neoplastic cells. Hence, directly targeting tumor-associated bacteria metabolites may have the potential to provide alternative and innovative strategies to bypass the gut microbiota for cancer therapy. As such, there are great opportunities to explore holistic approaches that incorporates TAB-derived metabolites and related metabolic signals modulation for cancer therapy. In this review, we will focus on key opportunistic areas by targeting TAB-derived metabolites and related metabolic signals, but not bacteria itself, for cancer treatment, and elucidate future challenges that need to be addressed in this emerging field.

Limited research has explored the association between dietary soy products and colorectal polyps and adenomas, with insufficient attention given to cooking methods and subtypes of polyps. This study aimed to comprehensively assess the relationship between soy intake, its cooking methods, and the risk of colorectal polyps and adenomas within a high-incidence population of colorectal cancer (CRC) in China.

Data were derived from 14,903 participants aged 40-80 years, enrolled in the extended Lanxi Pre-colorectal Cancer Cohort (LP3C) between March 2018 and December 2022. This cross-sectional study is based on the participants' baseline information. Long-term dietary information was collected through a validated food frequency questionnaire (FFQ), and colorectal polyps and adenomas were identified through electronic colonoscopy. Employing multivariate logistic regression, results were expressed as odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs).

4,942 cases of colorectal polyps and 2,678 cases of adenomas were ascertained. A significant positive association was found between total soy intake and the occurrence of polyps/adenomas. Considering cooking methods, a notable increase in polyp risk was associated with the consumption of fried soys while no association was detected for boiled or marinated soys. Furthermore, total soy intake demonstrated associations with large and multiple polyps, polyps Yamade-typed less than II, and polyps across all anatomical subsites.

Within the high-risk CRC population in China, increased soy product intake was linked to a higher risk of polyps, primarily attributed to the consumption of fried soys. This suggests that modifying cooking methods to avoid fried soys may serve as a preventive strategy for colorectal polyps.

Our study focuses on the microbial and metabolomic profile changes during the adenoma stage, as adenomas can be considered potential precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying possible intervention targets at this stage may aid in preventing the progression of colorectal adenoma (CRA) to malignant lesions. Furthermore, we evaluate the efficacy of combined microbial and metabolite biomarkers in detecting CRA.

Fecal metagenomic and serum metabolomic analyses were performed for the discovery of alterations of gut microbiome and metabolites in CRA patients (n = 26), Colorectal cancer (CRC) patients (n = 19), Familial Adenomatous Polyposis (FAP) patients (n = 10), and healthy controls (n = 20). Finally, analyzing the associations between gut microbes and metabolites was performed by a Receiver Operating Characteristic (ROC) curve.

Our analysis present that CRA patients differ significantly in gut microflora and serum metabolites compared with healthy controls, especially for Lachnospiraceae and Parasutterella. Its main metabolite, butyric acid, concentrations were raised in CRA patients compared with the healthy controls, indicating its role as a promoter of colorectal tumorigenesis. α-Linolenic acid and lysophosphatidylcholine represented the other healthy metabolite for CRA. Combining five microbial and five metabolite biomarkers, we differentiated CRA from CRC with an Area Under the Curve (AUC) of 0.85 out of this performance vastly superior to the specificity recorded by traditional markers CEA and CA199 in such differentiation of these conditions.

The study underlines significant microbial and metabolic alterations in CRA with a novel insight into screening and early intervention of its tumorigenesis.

Type 2 diabetes (T2DM) significantly diminishes people's quality of life and imposes a substantial economic burden. This pathological progression is intimately linked with specific gut microbiota, such as Akkermansia muciniphila. Pasteurized A. muciniphila (P-AKK) has been defined as a novel food by the European Food Safety Authority and exhibited significant hypoglycemic activity. However, current research on the hypoglycemic activity of P-AKK is limited to the metabolic level, neglecting systematic exploration at the pathological level. Consequently, its material basis and mechanism of action for hypoglycemia remain unclear. Drawing upon this foundation, we utilized high-temperature killed A. muciniphila (H-K-AKK) with insignificant hypoglycemic activity as the control research object. Assessments were conducted at pathological levels to evaluate the hypoglycemic functions of both P-AKK and H-K-AKK separately. Our study unveiled for the first time that P-AKK ameliorated symptoms of T2DM by enhancing the generation of glucagon-Like Peptide 1 (GLP-1), with pasteurized A. muciniphila total proteins (PP) being a pivotal component responsible for this activity. Utilizing SDS-PAGE, proteomics, and molecular docking techniques, we deeply analyzed the material foundation of PP. We scientifically screened and identified a protein weighing 77.85 kDa, designated as P5. P5 enhanced GLP-1 synthesis and secretion by activating the G protein-coupled receptor (GPCR) signaling pathway, with free fatty acid receptor 2 (FFAR-2) being identified as the pivotal target protein for P5's physiological activity. These findings further promote the widespread application of P-AKK in the food industry, laying a solid theoretical foundation for its utilization as a beneficial food ingredient or functional component.

The influence of gut microbiota in the onset and development of several metabolic diseases has gained attention over the last few years. Diet plays an essential role in gut microbiota modulation. Western diet (WD), characterized by high-sugar and high-fat consumption, alters gut microbiome composition, diversity index, microbial relative levels, and functional pathways. Despite the promising health effects demonstrated by polyunsaturated fatty acids, their impact on gut microbiota is still overlooked. The effect of Fish oil (omega-3 source) and Pomegranate oil (punicic acid source), and a mixture of both oils in gut microbiota modulation were determined by subjecting the oil samples to in vitro fecal fermentations. Cecal samples from rats from two different dietary groups: a control diet (CD) and a high-fat high-sugar diet (WD), were used as fecal inoculum. 16S amplicon metagenomics sequencing showed that Fish oil + Pomegranate oil from the WD group increased α-diversity. This sample can also increase the relative abundance of the Firmicutes and Bacteroidetes phylum as well as Akkermansia and Blautia, which were affected by the WD consumption. All samples were able to increase butyrate and acetate concentration in the WD group. Moreover, tyrosine concentrations, a precursor for dopamine and norepinephrine, increase in the Fish oil + Pomegranate oil WD sample. GABA, an important neurotransmitter, was also increased in WD samples. These results suggest a potential positive impact of these oils' mixture on gut-brain axis modulation. It was demonstrated, for the first time, the great potential of using a mixture of both Fish and Pomegranate oil to restore the gut microbiota changes associated with WD consumption.

Given the multitude of challenges Earth is facing, sustainability science is of key importance to our continued existence. Evolution is the fundamental biological process underlying the origin of all biodiversity. This phylogenetic diversity fosters the resilience of ecosystems to environmental change, and provides numerous resources to society, and options for the future. Genetic diversity within species is also key to the ability of populations to evolve and adapt to environmental change. Yet, the value of evolutionary processes and the consequences of their impairment have not generally been considered in sustainability research. We argue that biological evolution is important for sustainability and that the concepts, theory, data, and methodological approaches used in evolutionary biology can, in crucial ways, contribute to achieving the UN Sustainable Development Goals (SDGs). We discuss how evolutionary principles are relevant to understanding, maintaining, and improving Nature Contributions to People (NCP) and how they contribute to the SDGs. We highlight specific applications of evolution, evolutionary theory, and evolutionary biology's diverse toolbox, grouped into four major routes through which evolution and evolutionary insights can impact sustainability. We argue that information on both within-species evolutionary potential and among-species phylogenetic diversity is necessary to predict population, community, and ecosystem responses to global change and to make informed decisions on sustainable production, health, and well-being. We provide examples of how evolutionary insights and the tools developed by evolutionary biology can not only inspire and enhance progress on the trajectory to sustainability, but also highlight some obstacles that hitherto seem to have impeded an efficient uptake of evolutionary insights in sustainability research and actions to sustain SDGs. We call for enhanced collaboration between sustainability science and evolutionary biology to understand how integrating these disciplines can help achieve the sustainable future envisioned by the UN SDGs.

The gut microbiome (GMB) plays a substantial role in human health and disease. From affecting gut barrier integrity to promoting immune cell differentiation, the GMB is capable of shaping host immunity and thus oncogenesis and anti-cancer therapeutic response, particularly with immunotherapy. Dietary patterns and components are key determinants of GMB composition, supporting the investigation of the diet-microbiome-immunity axis as a potential avenue to enhance immunotherapy response in cancer patients. As such, this review will discuss the role of the GMB and diet on anti-cancer immunity. We demonstrate that diet affects anti-cancer immunity through both GMB-independent and GMB-mediated mechanisms, and that different diet patterns mold the GMB's functional and taxonomic composition in distinctive ways. Dietary modulation therefore shows promise as an intervention for improving cancer outcome; however, further and more extensive research in human cancer populations is needed.

The human gut flora comprises a dynamic network of bacterial species that coexist in a finely tuned equilibrium. The interaction with intestinal bacteria profoundly influences the host's development, metabolism, immunity, and overall health. Furthermore, dysbiosis, a disruption of the gut microbiota, can induce a variety of diseases, not exclusively associated with the intestinal tract. The increased consumption of animal protein, high-fat and high-sugar diets in Western countries has been implicated in the rise of chronic and inflammatory illnesses associated with dysbiosis. In particular, this diet leads to the overgrowth of sulfide-producing bacteria, known as sulfidogenic bacteria, which has been linked to inflammatory bowel diseases and colorectal cancer, among other disorders. Sulfidogenic bacteria include sulfate-reducing bacteria (Desulfovibrio spp.) and Bilophila wadsworthia among others, which convert organic and inorganic sulfur compounds to sulfide through the dissimilatory sulfite reduction pathway. At high concentrations, sulfide is cytotoxic and disrupts the integrity of the intestinal epithelium and mucus barrier, triggering inflammation. Besides producing sulfide, B. wadsworthia has revealed significant pathogenic potential, demonstrated in the ability to cause infection, adhere to intestinal cells, promote inflammation, and compromise the integrity of the colonic mucus layer. This review delves into the mechanisms by which taurine and sulfide-driven gut dysbiosis contribute to the pathogenesis of sulfidogenic bacteria, and discusses the role of these gut microbes, particularly B. wadsworthia, in human diseases.

Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of Phascolarctobacterium, Sutterella, and Streptococcus was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: Bacteroides_stercoris and Prevotella_copri. Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that Prevotella may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. Fusicatenibacter and Lachnospira may be involved in the degradation of indoles and derivatives. Alistipes, Agathobacter, and Parabacteroides may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that Prevotella, Alistipes, Agathobacter, and Parabacteroides might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.

Chronic kidney disease (CKD) is a widespread health concern, which affects ~9.1% of the global population and 12-15% of individuals in upper-middle income countries. Notably, ~2% of patients with CKD progress to end-stage renal disease (ESRD), which leads to a substantial decline in the quality of life, an increased risk of mortality and significant financial burden. Patients with ESRD often still suffer from uremia and uremic syndromes, due to the accumulation of toxins between dialysis sessions and the inadequate removal of protein-bound toxins during dialysis. A number of these toxins are produced by the gut microbiota through the fermentation of dietary proteins or cholines. Furthermore, the gut microbial community serves a key role in maintaining metabolic and immune equilibrium in individuals. The present study aimed to investigate the gut microbiota patterns in individuals with type 2 diabetes mellitus (T2DM) and ESRD via quantitative PCR analysis of the 16S and 18S ribosomal RNA of selected members of the gut microbiota. Individuals affected by both T2DM and ESRD displayed distinctive features within their intestinal microbiota. Specifically, there were increased levels of Gammaproteobacteria observed in these patients, and all subjects exhibited a notably increased presence of Enterobacteriaceae compared with healthy individuals. This particular microbial community has established connections with the presence of inflammatory processes in the colon. Moreover, the elevated levels of Enterobacteriaceae may serve as an indicator of an imbalance in the intestinal microbiota, a condition known as dysbiosis. In addition, the Betaproteobacteria phylum was significantly more prevalent in the stool samples of patients with both T2DM and ESRD when compared with the control group. In conclusion, the present pilot study focused on gut microbiome alterations in T2DM and ESRD. Understanding the relationship between dysbiosis and CKD may identify new areas of research and therapeutic interventions aimed at modulating the gut microbiota to improve the health and outcomes of individuals with CKD and ESRD.

Gut microbiota interacts with host epithelial cells and regulates many physiological functions such as genetics, epigenetics, metabolism of nutrients, and immune functions. Dietary factors may also be involved in the etiology of colorectal cancer (CRC), especially when an unhealthy diet is consumed with excess calorie intake and bad practices like smoking or consuming a great deal of alcohol. Bacteria including Fusobacterium nucleatum, Enterotoxigenic Bacteroides fragilis (ETBF), and Escherichia coli (E. coli) actively participate in the carcinogenesis of CRC. Gastrointestinal tract with chronic inflammation and immunocompromised patients are at high risk for CRC progression. Further, the gut microbiota is also involved in Geno-toxicity by producing toxins like colibactin and cytolethal distending toxin (CDT) which cause damage to double-stranded DNA. Specific microRNAs can act as either tumor suppressors or oncogenes depending on the cellular environment in which they are expressed. The current review mainly highlights the role of gut microbiota in CRC, the mechanisms of several factors in carcinogenesis, and the role of particular microbes in colorectal neoplasia.

It is now widely recognized that gut microbiota plays a critical role not only in the development and progression of diseases, but also in its susceptibility to dietary patterns, food composition, and nutritional intake. In this comprehensive review, we have compiled the latest findings on the effects of food nutrients and bioactive compounds on the gut microbiota. The research indicates that certain components, such as unsaturated fatty acids, dietary fiber, and protein have a significant impact on the composition of bile salts and short-chain fatty acids through catabolic processes, thereby influencing the gut microbiota. Additionally, these compounds also have an effect on the ratio of Firmicutes to Bacteroides, as well as the abundance of specific species like Akkermansia muciniphila. The gut microbiota has been found to play a role in altering the absorption and metabolism of nutrients, bioactive compounds, and drugs, adding another layer of complexity to the interaction between food and gut microbiota, which often requires long-term adaptation to yield substantial outcomes. In conclusion, understanding the relationship between food compounds and gut microbiota can offer valuable insights into the potential therapeutic applications of food and dietary interventions in various diseases and health conditions.

This study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency: infrequent (1-3 times/week, n = 4), mid-frequent (4-6 times/week, n = 7), and frequent (daily, n = 9). Utilizing 16S rRNA gene-based sequencing and LC-MS/MS metabolome profiling, significant differences in microbial diversity and community structures among the groups were observed. The infrequent group showed higher microbial diversity, with community structures significantly varying with defecation frequency, a pattern consistent across all sampling time points. The Ruminococcus genus was predominant in the infrequent group, but decreased with more frequent defecation, while the Bacteroides genus was more common in the frequent group, decreasing as defecation frequency lessened. The infrequent group demonstrated enriched biosynthesis genes for aromatic amino acids and branched-chain amino acids (BCAAs), in contrast to the frequent group, which had a higher prevalence of genes for BCAA catabolism. Metabolome analysis revealed higher levels of metabolites derived from aromatic amino acids and BCAA metabolism in the infrequent group, and lower levels of BCAA-derived metabolites in the frequent group, consistent with their predicted metagenomic functions. These findings underscore the importance of considering stool consistency/frequency in understanding the factors influencing the gut microbiome.

Transition from traditional high-fiber to Western diets in urbanizing communities of Sub-Saharan Africa is associated with increased risk of non-communicable diseases (NCD), exemplified by colorectal cancer (CRC) risk. To investigate how urbanization gives rise to microbial patterns that may be amenable by dietary intervention, we analyzed diet intake, fecal 16 S bacteriome, virome, and metabolome in a cross-sectional study in healthy rural and urban Xhosa people (South Africa). Urban Xhosa individuals had higher intakes of energy (urban: 3,578 ± 455; rural: 2,185 ± 179 kcal/d), fat and animal protein. This was associated with lower fecal bacteriome diversity and a shift from genera favoring degradation of complex carbohydrates (e.g., Prevotella) to taxa previously shown to be associated with bile acid metabolism and CRC. Urban Xhosa individuals had higher fecal levels of deoxycholic acid, shown to be associated with higher CRC risk, but similar short-chain fatty acid concentrations compared with rural individuals. Fecal virome composition was associated with distinct gut bacterial communities across urbanization, characterized by different dominant host bacteria (urban: Bacteriodota; rural: unassigned taxa) and variable correlation with fecal metabolites and dietary nutrients. Food and skin microbiota samples showed compositional differences along the urbanization gradient. Rural-urban dietary transition in South Africa is linked to major changes in the gut microbiome and metabolome. Further studies are needed to prove cause and identify whether restoration of specific components of the traditional diet will arrest the accelerating rise in NCDs in Sub-Saharan Africa.