The gut microbiota constitutes a complex ecosystem essential for host health, offering metabolic support, modulating the immune system, and protecting against pathogens. However, this community faces constant destabilizing challenges, including dietary changes, antibiotics, and enteric infection. Prolonged microbiota imbalance or dysbiosis can exacerbate intestinal disease states, including inflammatory bowel disease and colorectal cancer. Understanding the mechanisms that sustain microbiota resilience in the face of these imbalances is crucial for maintaining host health and developing effective therapeutics. This review explores microbiota resilience through the lens of an ecological model, emphasizing the interplay between microbial communities and host-driven environmental controls. We highlight two critical factors shaping microbiota resilience: oxygen tension and iron availability-challenges encountered by ancient anaerobic organisms during early evolutionary history, from which the predominant members of the microbiota have descended. Disruptions in intestinal anaerobiosis during inflammation increase luminal oxygen levels, favoring pro-inflammatory facultative anaerobes and depleting obligately anaerobic commensals. Simultaneously, host nutritional immunity restricts iron availability, further challenging commensal survival. This dual environmental challenge of rising oxygen tension and reduced iron availability is a convergent outcome of a diverse array of perturbations, from pathogen invasion to antibiotic treatment. By highlighting these conserved downstream environmental challenges rather than the specific upstream perturbations, this ecological view offers a focused framework for understanding microbiota resilience. This perspective not only enhances our understanding of host-microbiota interactions but also informs therapeutic strategies to foster resilience and support host health.

Food hydrogels targeting respiration of microorganisms via changing the micro-ecological environment in gut were prepared through the self-assembly of polyphenols extracted from tea leaves harvested in summer and autumn and the protein fibrils originating from egg white lysozyme. Oral administration with the hydrogels effectively inhibited the over-expansion of the facultative anaerobic bacterium indicated by E. coli Nissle 1917 (EcN) and alleviated the clinic symptoms of chronic intestinal inflammation in mice. Importantly, the hypoxia of epithelial cells was elevated significantly and the overexpression of the inducible NO synthase (INOs)-related NOS2 gene was inhibited substantially in colons of the colitis mice, which accounted for prevention of the abnormal expansion of E. coli via blocking respiration. The treatment with the hydrogels preserved normal mitochondrial function in colonic epithelial cells under oxidative stress, which could serve as the mechanism to maintain the capability to consume oxygen.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health vs IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

Hydrogen sulfide (H2S) is a gaseous gut metabolite with disputed effects on gastrointestinal health. Monitoring H2S concentration in the gut would provide insight into its role in disease but is complicated by sulfide's reactivity and volatility. Here we develop a transcriptional sulfide biosensor in Escherichiacoli. The sensor relies on enzymatic oxidation of sulfide catalyzed by a sulfide:quinone oxidoreductase (Sqr) to polysulfides, which interact with the repressor SqrR, triggering unbinding from the promoter and transcription of the reporter. Through promoter engineering and improved soluble SqrR expression, we optimized the system to provide an operational range of 50-750 μM and a dynamic range of 18 aerobically. To enable sensing in anaerobic environments, we identified an Sqr from Wolinella succinogenes that uses menaquinone, facilitating reoxidation through the anaerobic electron transport chain by fumarate or nitrate. Use of this homologue resulted in an anaerobic H2S response up to 750 μM. This sensor could ultimately enable spatially and temporally resolved measurements of H2S in the gastrointestinal tract to elucidate the role of this metabolite in disease and potentially as a noninvasive diagnostic.

The gut microbiota plays a crucial role in maintaining host health. While numerous studies have explored the impact of antibiotics on the gut microbiota in humans, limited research has examined how antibiotics affect the gut microbiome in dogs. This study investigated the effects of antibiotic treatment on the gut microbiota of dogs and assessed whether probiotic supplementation could prevent antibiotic-induced dysbiosis. Fourteen healthy young dogs undergoing castration were included in the study. All dogs received a single injection of cefovecin immediately after surgery. The probiotics group (7 dogs) was given a probiotic complex daily starting on the day of surgery and continuing for two weeks, while the non-probiotics group (7 dogs) received no supplementation. Fecal samples were collected on the day of surgery and two weeks later during the follow-up visit for suture removal for microbiome analysis. In microbial diversity analysis, α-diversity was significantly higher in the probiotic-supplemented group compared to the non-probiotics group (p < 0.05). β-diversity analysis revealed significant differences in microbial community composition in the non-probiotics group after antibiotic treatment (p < 0.05), while no significant differences were observed in the probiotics group. Relative abundance analysis indicated that Clostridioides, a marker of antibiotic-induced dysbiosis, significantly increased in dogs without probiotics after antibiotic treatment (p < 0.05). In contrast, Butyricicoccus, a butyrate-producing bacterium with gut health benefits, was significantly enriched in the probiotics group (p < 0.05). These findings suggest that probiotic supplementation supports healthier gut microbiome recovery following antibiotic treatment and highlights its potential to enhance gut microbiota restoration and mitigate gut dysbiosis caused by antibiotics.

Lipopolysaccharide (LPS), a component of the gram-negative bacteria cell well, is established to induce an acute and transient inflammatory cascade upon exogenous administration in mice, while negatively impacting aspects of the microbiota gut-brain axis (mGBA). Dietary supplementation with flaxseed (FS) has been shown to partially attenuate these impairments across the mGBA, although the importance of intestinal and hepatic health has not been established in this context. In this study, we furthered our investigation of the impact of dietary supplementation with FS and FS oil (FO) in mitigating LPS-induced perturbations to intestinal health (i.e. cecal microbiota, barrier integrity, inflammation, short-chain fatty acid (SCFA) production), hepatic inflammation, and their relationships to LPS-induced systemic and neuroinflammation. We noted distinct, diet-dependent shifts in the microbiota composition twenty-four hours post-LPS injection, that may be partially driven by the LPS-induced anorexia. BD-fed mice challenged with LPS showed reduced Muribaculaceae, while FS-LPS mice had elevated Akkermansia, and both the FS-LPS and FO-LPS mice had reduced Bacteroides, each with unique correlations to diet intake. These LPS-driven shifts in the microbiota were coupled with elevated ileal mucous content in the FS- and FO-fed mice, and intestinal inflammation which was partially attenuated in the FS-fed mice. Collectively, we highlight that FS modulates aspects of the intestinal microenvironment, which may be related to the anti-inflammatory effects across the mGBA.

We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD).

Participants with ulcerative colitis (UC), Crohn's disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling.

A total of 1404 individuals were included, where n = 1229 samples from adults were used in the main analyses (n = 658 UC, n = 324 CD, n = 36 IBD-U, n = 67 suspected IBD, and n = 144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P < .0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P = .008) and between colonic CD and UC (P = .005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P < .0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P < .0001).

Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.

Bacteriophages (phages) play a crucial role in shaping the composition and diversity of the human microbiome across various body niches. Recent advancements in high-throughput sequencing technologies have enabled comprehensive analysis of the human phageome in different body sites. This review comprehensively analyzes phage populations across major human body niches, examining their distribution and dynamics through recent metagenomic discoveries. We explore how phage-bacteria interactions within different body sites contribute to homeostasis and disease development. Emerging evidence demonstrates that phageome perturbations can serve as early indicators of various disorders, particularly in the gut microbiome. Understanding these complex microbial interactions offers promising opportunities for developing novel diagnostic markers and therapeutic approaches. However, the causal relationship between phages, bacteria, and disease development remains unclear. Further research is needed to elucidate the role of phages in human health and disease and to explore their potential as diagnostic or therapeutic tools. Understanding the intricate interactions between phages, bacteria, and the human host is crucial for unraveling the complexities of the human microbiome and its impact on health and disease.

Artificial sweeteners have emerged as popular alternatives to traditional sweeteners, driven by the growing concern over sugar consumption and its associated rise in obesity and metabolic disorders. Despite their widespread use, the safety and health implications of artificial sweeteners remain a topic of debate, with conflicting evidence contributing to uncertainty about their long-term effects. This review synthesizes current scientific evidence regarding the impact of artificial sweeteners on gut microbiota and gastrointestinal health. Our analysis of in vitro experiments, animal models, and clinical trials reveals that artificial sweeteners can alter the composition and abundance of gut microbes. These changes raise concerns about their potential to affect overall gut health and contribute to gastrointestinal disorders. Additionally, artificial sweeteners have been shown to influence the production of metabolites by gut bacteria, further impacting systemic health. The findings suggest that artificial sweeteners may have complex and sometimes contradictory effects on gut microbiota. While some studies indicate potential benefits, such as reduced caloric intake and weight management, others highlight detrimental effects on microbial balance and metabolic functions. The inconsistent results underscore the need for further research to comprehensively understand the physiological impacts of various artificial sweeteners on human health. Future studies should aim for long-term, well-controlled investigations to clarify these relationships, ensuring evidence-based guidelines for the safe use of artificial sweeteners in diet management. © 2025 Society of Chemical Industry.

Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development and progression of chronic diseases. This review provides a comprehensive analysis of the complex interplay between these two factors, focusing on how an imbalance between reactive oxygen species (ROS) and antioxidants leads to OS, disrupting cellular homeostasis and contributing to a range of conditions, including metabolic disorders, cardiovascular diseases, neurological diseases, and cancer. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, is essential for regulating immune responses, metabolic pathways, and overall health. Dysbiosis, an imbalance in the gut microbiota composition, is closely associated with chronic inflammation, metabolic dysfunction, and various diseases. This review highlights how the gut microbiota influences and is influenced by OS, complicating the pathophysiology of many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators of cellular crosstalk between the OS and gut microbiota. EVs also play a crucial role in signaling between the gut microbiota and host tissues, modulating immune responses, inflammation, and metabolic processes. The signaling function of EVs holds promise for the development of targeted therapies aimed at restoring microbial balance and mitigating OS. Personalized therapeutic approaches, including probiotics, antioxidants, and fecal microbiota transplantation-based strategies, can be used to address OS-related diseases and improve health outcomes. Nonetheless, further research is needed to study the molecular mechanisms underlying these interactions and the potential of innovative interventions to offer novel strategies for managing OS-related diseases and enhancing overall human health.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.

Inflammatory bowel disease (IBD) is characterized by disruptions in the gut microbiome. While most studies on gut dysbiosis in IBD rely on sequencing-based methods, we employed a streamlined culturomics approach to obtain a more comprehensive understanding of gut microbiota imbalance in patients with IBD that may not be captured by sequencing alone. A total of 367 bacteria were identified at the species level, including 211 species from ulcerative colitis patients, 164 species from Crohn's disease (CD) patients, and 263 species from healthy individuals. Consistent with our 16S rRNA gene amplicon sequencing results, a significant decrease in microbial diversity and a severe imbalance, especially in CD patients, were also observed in the culture-based analysis. Our culturomics approach provided additional insights, highlighting dysbiosis in unique anaerobic and Gram-negative species in CD patients. Moreover, species-level findings for Bifidobacterium and Enterobacterales emphasized specific species expansions in IBD patients. Notably, Mediterraneibacter gnavus, Thomasclavelia ramosa, Parabacteroides merdae, and Collinsella aerofaciens are of particular clinical interest due to their correlation with inflammatory biomarkers. This comprehensive analysis underscores the value of integrating a culture-based approach with a genome-based approach to provide complementary insights and therapeutic targets in IBD.

Hydrogen sulfide (H2S) is a gaseous gut metabolite with disputed effects on gastrointestinal health. Monitoring H2S concentration in the gut would provide insight into its role in disease, but is complicated by sulfide's reactivity and volatility. Here we develop a transcriptional sulfide biosensor in E. coli. The sensor relies on enzymatic oxidation of sulfide catalyzed by a sulfide:quinone reductase (Sqr) to polysulfides, which bind to the repressor SqrR, triggering unbinding from the promoter and transcription of the reporter. Through promoter engineering and improving soluble SqrR expression, we optimized the system to provide an operational range of 50 μM - 750 μM and dynamic range of 18 aerobically. To enable sensing in anaerobic environments, we identified an Sqr from Wolinella succinogenes that uses menaquinone, facilitating reoxidation through the anaerobic electron transport chain by fumarate or nitrate. Use of this homolog resulted in an anaerobic H2S response up to 750 μM. This sensor could ultimately enable spatially and temporally resolved measurements of H2S in the gastrointestinal tract to elucidate the role of this metabolite in disease, and potentially as a non-invasive diagnostic.

Enterocolitis is a common and potentially deadly manifestation of Hirschsprung disease (HSCR) but disease mechanisms remain poorly defined. Unexpectedly, we discovered that diet can dramatically affect the lifespan of a HSCR mouse model ( Piebald lethal , sl/sl ) where affected animals die from HAEC complications. In the sl/sl model, diet alters gut microbes and metabolites, leading to changes in colon epithelial gene expression and epithelial oxygen levels known to influence colitis severity. Our findings demonstrate unrecognized similarity between HAEC and other types of colitis and suggest dietary manipulation could be a valuable therapeutic strategy for people with HSCR.

Hirschsprung disease (HSCR) is a birth defect where enteric nervous system (ENS) is absent from distal bowel. Bowel lacking ENS fails to relax, causing partial obstruction. Affected children often have "Hirschsprung disease associated enterocolitis" (HAEC), which predisposes to sepsis. We discovered survival of Piebald lethal ( sl/sl ) mice, a well-established HSCR model with HAEC, is markedly altered by two distinct standard chow diets. A "Protective" diet increased fecal butyrate/isobutyrate and enhanced production of gut epithelial antimicrobial peptides in proximal colon. In contrast, "Detrimental" diet-fed sl/sl had abnormal appearing distal colon epithelium mitochondria, reduced epithelial mRNA involved in oxidative phosphorylation, and elevated epithelial oxygen that fostered growth of inflammation-associated Enterobacteriaceae . Accordingly, selective depletion of Enterobacteriaceae with sodium tungstate prolonged sl/sl survival. Our results provide the first strong evidence that diet modifies survival in a HSCR mouse model, without altering length of distal colon lacking ENS.

Two different standard mouse diets alter survival in the Piebald lethal ( sl/sl ) mouse model of Hirschsprung disease, without impacting extent of distal colon aganglionosis (the region lacking ENS). Piebald lethal mice fed the "Detrimental" diet had many changes in colon epithelial transcriptome including decreased mRNA for antimicrobial peptides and genes involved in oxidative phosphorylation. Detrimental diet fed sl/sl also had aberrant-appearing mitochondria in distal colon epithelium, with elevated epithelial oxygen that drives lethal Enterobacteriaceae overgrowth via aerobic respiration. Elimination of Enterobacteriaceae with antibiotics or sodium tungstate improves survival of Piebald lethal fed the "Detrimental diet".

Macrophyte-based lake restoration has successfully transitioned lakes from turbid conditions dominated by phytoplankton to a more natural, clear state; however, its impact on microbial carbon pump-mediated dissolved organic carbon (DOM) storage and greenhouse gas (GHG) emissions in the aquatic ecosystem remains largely unexplored. Through a year-long field study, we conducted a comparative analysis of two alternative habitats within the same lake-restored and unrestored areas. Results demonstrated that restoration not only substantially decreases nutrient levels and algal blooms-evidenced by over 50% reductions in nitrogen, phosphorus, and chlorophyll a-but also significantly increases the accumulation of recalcitrant DOM. This is characterized by rises of 9.52% in highly unsaturated compounds, 8.68% in carboxyl-rich alicyclic molecules, 37.54% polycyclic condensed aromatics and polyphenols, and 20.21% in SUVA254. Additionallly, key microbial taxa with potent carbon pump functions-primarily Gammaproteobacteria, Alphaproteobacteria, and Actinobacteria-are enriched in restored areas. Structural equation modeling (SEM) further elucidated the complex interrelationships within more pristine lake ecosystems: macrophytes and elevated dissolved oxygen (DO) concentrations enhance carbon sequestration via microbial carbon pump pathways, while the restoration significantly mitigates methane emissions caused by eutrophication. These findings highlight an extra function of aquatic macrophyte restoration, offering valuable insights into microbial processes for future restoration efforts aimed at promoting sustainable aquatic ecosystems and mitigating global warming.

The gut microbiome affects the occurrence and development of metabolic diseases, with a significant amount of research focused on intestinal bacteria. As an important part of the gut microbiome, gut viruses were studied recently, particularly through fecal virome transplantation (FVT), revealing manipulating the gut virus could reverse overweight and glucose intolerance in mice. And human cohort studies found gut virome changed significantly in patients with metabolic disease. By summarizing those studies, we compared the research and analytical methods, as well as the similarities and differences in their results, and analyzed the reasons for these discrepancies. FVT provided potential value to improve metabolic diseases, but the mechanisms involved and the effect of FVT on humans should be investigated further. The potential methods of regulating intestinal virome composition and the possible mechanisms of intestinal virome changes affecting metabolic diseases were also discussed.

The term "gut microbiota" primarily refers to the ecological community of various microorganisms in the gut, which constitutes the largest microbial community in the human body. Although adequate bowel preparation can improve the results of colonoscopy, it may interfere with the gut microbiota. Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota, potentially affecting an individual's health, especially in vulnerable populations, such as patients with inflammatory bowel disease. However, measures such as oral probiotics may ameliorate these adverse effects. We focused on the bowel preparation-induced changes in the gut microbiota and host health status, hypothesized the factors influencing these changes, and attempted to identify measures that may reduce dysbiosis, thereby providing more information for individualized bowel preparation for colonoscopy in the future.

The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals that mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. The natural history of IBD progression begins with early subclinical stages of disease that occur before clinical diagnosis. Improved understanding of those early subclinical stages could lead to new or improved strategies for IBD diagnosis, prognostication, or prevention. Here, we review our current understanding of the early subclinical stages of IBD in humans including studies from first-degree relatives of patients with IBD and members of the general population who go on to develop IBD. We also discuss representative mouse models of IBD that can be used to investigate disease dynamics and host-microbiota relationships during these early stages. In particular, we underscore how mouse models of IBD that develop disease later in life with variable penetrance may present valuable opportunities to discern early subclinical mechanisms of disease before histological inflammation and other severe symptoms become apparent.

Major depressive disorder (MDD) is defined as mood disorder causing a persistent loss of interest and despair for two weeks or greater, with related symptoms. Depression can interfere with daily life and can cause those affected to not work, study, eat, sleep, and enjoy previously enjoyed hobbies and life events as they did previously. If untreated, it can become a serious health condition. Depression is multifactorial with a variety of factors influencing the condition. These factors include: (1) poor diet and exercise, (2) socioeconomic status, (3) gender, (4) biological clocks, (5) genetics and epigenetics, and (6) personal stressors. Treatment of depressive disorders is thus also multifactorial and utilizes the following therapies: (1) diet and exercise, (2) bright light therapy, (3) cognitive behavioral therapy, and (4) pharmaceutical therapy. Obesity is defined as body mass index over 30 and above, is believed to be causally linked to MDD through both psychological and molecular means. Atypical depression, a common form of MDD, is most strongly correlated with a high proclivity for obesity. Obesity and depression have a bidirectional relationship, a patient experiencing either condition singularly is more likely to develop the other due to the neural links between the two, including emotional lability, physical health of the brain, hormones, cytokine secretion, appetite, diet and feeding habits, inflammatory state. In individuals consuming a high fat diet (HFD) commonly ingested by those with obesity, the gut-microbiome is altered leading to systemic inflammation and the dysregulation of mood and the HPA axis impacting their neural health. The purpose of this paper is to examine the interplay of potential molecular, psychological, societal, and environmental causal factors of depressive disorders and how obesity perpetuates depression. A secondary aim of this paper is to examine current interventions that may help improve those affected by both conditions.

(1) Background: This study evaluated the effects of BiotiQuest® Sugar Shift®, a novel probiotic formulation, for its impact on gut microbiome composition and metabolic health in type 2 diabetes mellitus (T2D). T2D is characterized by chronic inflammation and gut microbiome imbalances, yet the therapeutic potential of targeted probiotics remains underexplored. (2) Methods: In a 12-week randomized, double-blind, placebo-controlled trial, 64 adults with T2D received either Sugar Shift or placebo capsules twice daily. Each dose provided 18 billion CFU of eight GRAS-certified bacterial strains and prebiotics. Clinical samples were analyzed for metabolic markers, and microbiome changes were assessed using 16S rRNA sequencing and metagenomics. (3) Results: Sugar Shift significantly reduced serum lipopolysaccharide (LPS) levels, improved insulin sensitivity (lower HOMA-IR scores), and increased short-chain fatty acid (SCFA)-producing genera, including Bifidobacterium, Faecalibacterium, Fusicatenibacter, and Roseburia. Pro-inflammatory taxa like Enterobacteriaceae decreased, with reduced LPS biosynthesis genes and increased SCFA production genes. The Lachnospiraceae:Enterobactericeae ratio emerged as a biomarker of reduced inflammation. (4) Conclusions: These findings demonstrate the potential of Sugar Shift to restore gut homeostasis, reduce inflammation, and improve metabolic health in T2D. Further studies are warranted to explore its long-term efficacy and broader application in metabolic disease management.

Colorectal cancer (CRC), with a growing incidence trend, is one of the most diagnosed cancers and the second cause of cancer-related deaths worldwide. The literature has frequently focused attention on the correlation between the gut microbiota imbalance and CRC. The genera Lactobacillus and Bifidobacterium have recently received increasing attention because of their potential in restoring alterations in the gut microflora. Therefore, this study aimed to quantitatively evaluate the presence of lactobacilli and bifidobacterial strains in the fecal samples of CRC patients compared to healthy volunteers.

From 2018 to 2019, 25 confirmed CRC patients and 25 age- and gender-matched control subjects were enrolled in the study. Bacterial DNA was extracted from the fecal samples and the presence of lactobacilli and bifidobacterial strains were quantitatively determined using quantitative real-time PCR using genus-specific 16S rDNA primers.

A significant decline in the abundance of bifidobacteria in CRC patients compared to healthy individuals (p value<0.003) was observed; however, no significant difference was observed between the two groups regarding the abundance of lactobacilli (p value<0.163). Correlation analysis showed a positive association between the lack of genetic history of CRC and the numbers of gut bifidobacteria and lactobacilli.

As a putative gut probiotic, depletion of bifidobacteria showed significant correlation to the development and progression of CRC; therefore, therapeutic use of these probiotic bacteria could be considered a possible adjuvant approach in disease management through modulation of the microbiota.

The gut microbiome, composed of the colonic microbiota and their host environment, is important for many aspects of human health. A gut microbiome imbalance (gut dysbiosis) is associated with major causes of human morbidity and mortality. Despite the central part our gut microbiome plays in health and disease, mechanisms that maintain homeostasis and properties that demarcate dysbiosis remain largely undefined. Here we discuss that sorting taxa into meaningful ecological units reveals that the availability of respiratory electron acceptors, such as oxygen, in the host environment has a dominant influence on gut microbiome health. During homeostasis, host functions that limit the diffusion of oxygen into the colonic lumen shelter a microbial community dominated by primary fermenters from atmospheric oxygen. In turn, primary fermenters break down unabsorbed nutrients into fermentation products that support host nutrition. This symbiotic relationship is disrupted when host functions that limit the luminal availability of host-derived electron acceptors become weakened. The resulting changes in the host environment drive alterations in the microbiota composition, which feature an elevated abundance of facultatively anaerobic microbes. Thus, the part of the gut microbiome that becomes imbalanced during dysbiosis is the host environment, whereas changes in the microbiota composition are secondary to this underlying cause. This shift in our understanding of dysbiosis provides a novel starting point for therapeutic strategies to restore microbiome health. Such strategies can either target the microbes through metabolism-based editing or strengthen the host functions that control their environment.

It is unknown if gastrointestinal dysbiosis in diarrheic calves causes disease or is a consequence of the disease.

Describe the fecal microbiota of calves before, during, and after recovering from diarrhea.

Fifteen female Holstein calves of 0 to 21 days old from a single farm. Seven calves remained healthy throughout the study, and 8 developed diarrhea on Day 14.

Longitudinal cohort study. Microbiota composition was characterized by amplifying the V4 region of the 16S rRNA gene.

Diversity (Shannon index) increased with age in healthy and diarrheic calves from Day 3 to 21, but diarrheic calves had a lower diversity on the day diarrhea was first observed (Day 14). By Day 21, diversity increased in calves that recovered from diarrhea and was not significantly different from that of their healthy counterparts (P > .05). Weighted UniFrac distance showed significant differences in the fecal microbiota between diarrheic and healthy calves at Day 14 of age (PERMANOVA, P < .05), but not before or after diarrhea (PERMANOVA, P > .05). Lactobacillus, Clostridium Sensu Stricto 1, and Collinsella were differentially abundant on Day 10 in calves that developed diarrhea on Day 14 (P < .05).

The fecal microbiota of healthy and diarrheic calves evolved similarly during the first 10 days of age but differed significantly on the day of onset of diarrhea. Enriching Lactobacillus, Clostridium Sensu Stricto 1, and Collinsella before diarrhea onset could have been contributed to the development of diarrhea.

Grain bran dietary fiber (DF) has the effect of promoting intestinal health and is worth being studied. In the present study, the physicochemical properties and prevention effect of DF on ulcerative colitis (UC) were investigated. The results showed that the optimal extraction conditions were determined as α-amylase (350 U/g, 70 °C, pH 7.0, 2.5 h) and papain (100 U/g, 60 °C, pH 7.0, 1.5 h), resulting in a yield of 83.81% for DF. Moreover, DF exhibited unique physicochemical properties contributing to its preventive effects, as evidenced by its ability to mitigate symptoms such as hematochezia, immune inflammation, and impaired intestinal barrier in UC mice. The underlying mechanism can be attributed to the regulation of phenylalanine, tyrosine and tryptophan biosynthesis pathway and maintenance of intestinal microbial homeostasis. Therefore, our study suggests that grain bran DF holds potential for the prevention of UC, providing a basis for the development and utilization of grain bran.

Crohn's disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry.

At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs.

The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract.

This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes.

In this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls.

Significant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently.

Our findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies.

Food protein-induced enterocolitis syndrome (FPIES) is a severe type of non-IgE (immunoglobulin E)-mediated (NIM) food allergy, with cow's milk (CM) being the most common offending food. The relationship between the gut microbiota and its metabolites with the inflammatory process in infants with CM FPIES is unknown, although evidence suggests a microbial dysbiosis in NIM patients. This study was performed to contribute to the knowledge of the interaction between the gut microbiota and its derived metabolites with the local immune system in feces of infants with CM FPIES at diagnosis.

Twelve infants with CM FPIES and a matched healthy control group were recruited and the gut microbiota was investigated by 16S amplicon and shotgun sequencing. Fatty acids (FAs) were measured by gas chromatography, while immune factors were determined by enzyme-linked immunosorbent assay and Luminex technology.

A specific pattern of microbiota in the gut of CM FPIES patients was found, characterized by a high abundance of enterobacteria. Also, an intense excretion of FAs in the feces of these infants was observed. Furthermore, correlations were found between fecal bifidobacteria and immune factors.

These fecal determinations may be useful to gain insight into the pathophysiology of this syndrome and should be taken in consideration for future studies of FPIES patients.

Since dietary intake is challenging to directly measure in large-scale cohort studies, we often rely on self-reported instruments (e.g., food frequency questionnaires, 24-hour recalls, and diet records) developed in nutritional epidemiology. Those self-reported instruments are prone to measurement errors, which can lead to inaccuracies in the calculation of nutrient profiles. Currently, few computational methods exist to address this problem. In the present study, we introduce a deep-learning approach --- Microbiome-based nutrient profile corrector (METRIC), which leverages gut microbial compositions to correct random errors in self-reported dietary assessments using 24-hour recalls or diet records. We demonstrate the excellent performance of METRIC in minimizing the simulated random errors, particularly for nutrients metabolized by gut bacteria in both synthetic and three real-world datasets. Further research is warranted to examine the utility of METRIC to correct actual measurement errors in self-reported dietary assessment instruments.

Mammalian cells utilize glucose as a primary carbon source to produce energy for most cellular functions. However, the bioenergetic homeostasis of cells can be perturbed by environmental alterations, such as changes in oxygen levels which can be associated with bacterial infection. Reduction in oxygen availability leads to a state of hypoxia, inducing numerous cellular responses that aim to combat this stress. Importantly, hypoxia strongly augments cellular glycolysis in most cell types to compensate for the loss of aerobic respiration. Understanding how this host cell metabolic adaptation to hypoxia impacts the course of bacterial infection will identify new anti-microbial targets. This review will highlight developments in our understanding of glycolytic substrate channeling and spatiotemporal enzymatic organization in response to hypoxia, shedding light on the integral role of the hypoxia-inducible factor (HIF) during host-pathogen interactions. Furthermore, the ability of intracellular and extracellular bacteria (pathogens and commensals alike) to modulate host cellular glucose metabolism will be discussed.

H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota.

Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives.

Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract.

Systemic lupus erythematosus is a complex autoimmune disease resulting from a dysregulation of the immune system that involves gut dysbiosis and an altered host cellular metabolism. This review highlights novel insights and expands on the interactions between the gut microbiome and the host immune metabolism in lupus. Pathobionts, invasive pathogens, and even commensal microbes, when in dysbiosis, can all trigger and modulate immune responses through metabolic reprogramming. Changes in the microbiota's global composition or individual taxa may trigger a cascade of metabolic changes in immune cells that may, in turn, reprogram their functions. Factors contributing to dysbiosis include changes in intestinal hypoxia, competition for glucose, and limited availability of essential nutrients, such as tryptophan and metal ions, all of which can be driven by host metabolism changes. Conversely, the accumulation of some host metabolites, such as itaconate, succinate, and free fatty acids, could further influence the microbial composition and immune responses. Overall, mounting evidence supports a bidirectional relationship between host immunometabolism and the microbiota in lupus pathogenesis.

A fiber-rich diet is considered beneficial for gut health. An inflamed gut with a dysbiotic bacterial community can result in altered fiber metabolism depending on the fiber's physicochemical properties. This study examined the effect of fiber's physicochemical properties on fiber fermentation in the presence of healthy and colitis-associated bacteria. Sixteen fibers with different levels of solubility, complexity, and fermentation rate were used in in vitro fermentation with healthy human gut bacteria. Resistant maltodextrins (RMD), pectin (HMP), inulin (ChIn), and wheat bran (WB) were selected for fermentation using ulcerative colitis (UC)-associated bacteria to assess bacterial dysbiosis effect. UC-associated gut microbiota showed a significant reduction in α-and β-diversity indices compared to healthy-associated microbiota. The differences in the gut microbiota composition and diversity between the donors resulted in decreased fermentation rates with UC-associated bacteria. Fiber fermentation metabolites, short-chain fatty acids (SCFA) and gas production were significantly lower in the presence of UC-associated bacteria for all four fibers tested. Overall, we conclude that dietary fiber properties and microbial dysbiosis are influential in fiber fermentation and metabolite production in the gut.

The relative abundances of Bacteroidetes and Fusobacteria phyla have been reported to be decreased in dogs with chronic enteropathies. In colitis, obligate anaerobes (e.g., Bacteroides and Fusobacterium) are likely to vanish in response to the heightened oxidative stress in the colon's inflammatory environment. The ability to adhere to the colonic mucosa is viewed as an essential step for obligate anaerobic bacteria to colonize and subsequently interact with the host's epithelium and immune system. The reintroduction of a balanced community of obligate anaerobic bacteria using probiotics can restore the microbial function in the intestine. We found no studies on dogs regarding the adhesion properties of Bacteriodes vulgatus and Fusobacterium varium on paraffin-embedded canine colonic mucosa. Thus, the objective of this study is to investigate the adhesion capacities of these two bacterial species to paraffin-embedded colonic mucosa from healthy dogs. Additionally, we investigated their hydrophobicity properties to determine whether differences in adhesion capability can be explained by this factor. The results of our study showed that B. vulgatus adhered significantly lower than F. varium to the canine colonic mucosa (p = 0.002); however, B. vulgatus showed higher hydrophobicity (46.1%) than F. varium (12.6%). In conclusion, both bacteria have potential as probiotics, but further studies will be required to determine the efficacy and safety of the strains to be used, which strains to use, and the reasons other than hydrophobicity for attachment.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and a leading cause of neurological disability in young adults. Clinical presentation and disease course are highly heterogeneous. Typically, disease progression occurs over time and is characterized by the gradual accumulation of disability. The risk of developing MS is driven by complex interactions between genetic and environmental factors, including the gut microbiome. How the commensal gut microbiota impacts disease severity and progression over time remains unknown. In a longitudinal study, disability status and associated clinical features in 58 MS patients were tracked over 4.2 ± 0.98 years, and the baseline fecal gut microbiome was characterized via 16S amplicon sequencing. Progressor status, defined as patients with an increase in Expanded Disability Status Scale (EDSS), were correlated with features of the gut microbiome to determine candidate microbiota associated with risk of MS disease progression. We found no overt differences in microbial community diversity and overall structure between MS patients exhibiting disease progression and non-progressors. However, a total of 41 bacterial species were associated with worsening disease, including a marked depletion in Akkermansia, Lachnospiraceae, and Oscillospiraceae, with an expansion of Alloprevotella, Prevotella-9, and Rhodospirillales. Analysis of the metabolic potential of the inferred metagenome from taxa associated with progression revealed enrichment in oxidative stress-inducing aerobic respiration at the expense of microbial vitamin K2 production (linked to Akkermansia), and a depletion in SCFA metabolism (linked to Oscillospiraceae). Further, as a proof of principle, statistical modeling demonstrated that microbiota composition and clinical features were sufficient to predict disease progression. Additionally, we found that constipation, a frequent gastrointestinal comorbidity among MS patients, exhibited a divergent microbial signature compared with progressor status. These results demonstrate a proof of principle for the utility of the gut microbiome for predicting disease progression in MS in a small well-defined cohort. Further, analysis of the inferred metagenome suggested that oxidative stress, vitamin K2, and SCFAs are associated with progression, warranting future functional validation and mechanistic study.

Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors and responds to such changes remains unclear. Here, we describe a protective mechanism by which mucosal-associated invariant T (MAIT) cells detect microbiota metabolites produced upon intestinal inflammation and promote tissue repair. At steady state, MAIT ligands derived from the riboflavin biosynthesis pathway were produced by aerotolerant bacteria residing in the colonic mucosa. Experimental colitis triggered luminal expansion of riboflavin-producing bacteria, leading to increased production of MAIT ligands. Modulation of intestinal oxygen levels suggested a role for oxygen in inducing MAIT ligand production. MAIT ligands produced in the colon rapidly crossed the intestinal barrier and activated MAIT cells, which expressed tissue-repair genes and produced barrier-promoting mediators during colitis. Mice lacking MAIT cells were more susceptible to colitis and colitis-driven colorectal cancer. Thus, MAIT cells are sensitive to a bacterial metabolic pathway indicative of intestinal inflammation.