Diet affects multiple facets of human health and is inextricably linked to chronic metabolic conditions such as obesity, type 2 diabetes, and cardiovascular disease. Dietary nutrients are essential ...not only for human health but also for the health and survival of the trillions of microbes that reside within the human intestines. Diet is a key component of the relationship between humans and their microbial residents; gut microbes use ingested nutrients for fundamental biological processes, and the metabolic outputs of those processes may have important impacts on human physiology. Studies in humans and animal models are beginning to unravel the underpinnings of this relationship, and increasing evidence suggests that it may underlie some of the broader effects of diet on human health and disease.
In this study we used stool profiling to identify intestinal bacteria and metabolites that are differentially represented in humans with colorectal cancer (CRC) compared to healthy controls to ...identify how microbial functions may influence CRC development. Stool samples were collected from healthy adults (n = 10) and colorectal cancer patients (n = 11) prior to colon resection surgery at the University of Colorado Health-Poudre Valley Hospital in Fort Collins, CO. The V4 region of the 16s rRNA gene was pyrosequenced and both short chain fatty acids and global stool metabolites were extracted and analyzed utilizing Gas Chromatography-Mass Spectrometry (GC-MS). There were no significant differences in the overall microbial community structure associated with the disease state, but several bacterial genera, particularly butyrate-producing species, were under-represented in the CRC samples, while a mucin-degrading species, Akkermansia muciniphila , was about 4-fold higher in CRC (p<0.01). Proportionately higher amounts of butyrate were seen in stool of healthy individuals while relative concentrations of acetate were higher in stools of CRC patients. GC-MS profiling revealed higher concentrations of amino acids in stool samples from CRC patients and higher poly and monounsaturated fatty acids and ursodeoxycholic acid, a conjugated bile acid in stool samples from healthy adults (p<0.01). Correlative analysis between the combined datasets revealed some potential relationships between stool metabolites and certain bacterial species. These associations could provide insight into microbial functions occurring in a cancer environment and will help direct future mechanistic studies. Using integrated “omics” approaches may prove a useful tool in identifying functional groups of gastrointestinal bacteria and their associated metabolites as novel therapeutic and chemopreventive targets.
Interactions between the microbiota and distal gut are fundamental determinants of human health. Such interactions are concentrated at the colonic mucosa and provide energy for the host epithelium ...through the production of the short-chain fatty acid butyrate. We sought to determine the role of epithelial butyrate metabolism in establishing the austere oxygenation profile of the distal gut. Bacteria-derived butyrate affects epithelial O2 consumption and results in stabilization of hypoxia-inducible factor (HIF), a transcription factor coordinating barrier protection. Antibiotic-mediated depletion of the microbiota reduces colonic butyrate and HIF expression, both of which are restored by butyrate supplementation. Additionally, germ-free mice exhibit diminished retention of O2-sensitive dyes and decreased stabilized HIF. Furthermore, the influences of butyrate are lost in cells lacking HIF, thus linking butyrate metabolism to stabilized HIF and barrier function. This work highlights a mechanism where host-microbe interactions augment barrier function in the distal gut.
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•The mammalian colon exists in a state of relative hypoxia•Hypoxic regions of the normal colon provide a signaling axis through HIF-1•Microbial-derived butyrate depletes O2 and activates HIF-1•Microbiota-derived butyrate is barrier-protective in the mucosa
Decreased short-chain fatty acid (SCFA) production by the microbiota has been correlated with colonic inflammation and disease. Kelly et al. show that microbial-derived SCFAs, particularly butyrate, stimulate epithelial metabolism and deplete intracellular O2, resulting in stabilization of the transcription factor HIF-1 and increased epithelial barrier function.
The gut microbiome has emerged as a critical regulator of human physiology. Deleterious changes to the composition or number of gut bacteria, commonly referred to as gut dysbiosis, has been linked to ...the development and progression of numerous diet-related diseases, including cardiovascular disease (CVD). Most CVD risk factors, including aging, obesity, certain dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites that may facilitate the development of CVD. The aim of the current review is to summarize the available data regarding the role of the gut microbiome in regulating CVD function and disease processes. Particular emphasis is placed on nutrition-related alterations in the microbiome, as well as the underlying cellular mechanisms by which the microbiome may alter CVD risk.
Edible insects are often considered a nutritious, protein-rich, environmentally sustainable alternative to traditional livestock with growing popularity among North American consumers. While the ...nutrient composition of several insects is characterized, all potential health impacts have not been evaluated. In addition to high protein levels, crickets contain chitin and other fibers that may influence gut health. In this study, we evaluated the effects of consuming 25 grams/day whole cricket powder on gut microbiota composition, while assessing safety and tolerability. Twenty healthy adults participated in this six-week, double-blind, crossover dietary intervention. Participants were randomized into two study arms and consumed either cricket-containing or control breakfast foods for 14 days, followed by a washout period and assignment to the opposite treatment. Blood and stool samples were collected at baseline and after each treatment period to assess liver function and microbiota changes. Results demonstrate cricket consumption is tolerable and non-toxic at the studied dose. Cricket powder supported growth of the probiotic bacterium, Bifidobacterium animalis, which increased 5.7-fold. Cricket consumption was also associated with reduced plasma TNF-α. These data suggest that eating crickets may improve gut health and reduce systemic inflammation; however, more research is needed to understand these effects and underlying mechanisms.
Type 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium ...glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism. The aim of the current study was to examine if dapagliflozin, a widely prescribed STLT2i, improves generalized vascular dysfunction in type 2 diabetic mice. In light of several studies demonstrating a bi-directional relation between orally ingested medications and the gut microbiota, a secondary aim was to determine the effects of dapagliflozin on the gut microbiota.
Male diabetic mice (Db, n = 24) and control littermates (Con; n = 23) were randomized to receive either a standard diet or a standard diet containing dapagliflozin (60 mg dapagliflozin/kg diet; 0.006%) for 8 weeks. Arterial stiffness was assessed by aortic pulse wave velocity; endothelial function and vascular smooth muscle dysfunction were assessed by dilatory responses to acetylcholine and sodium nitroprusside, respectively.
Compared to untreated diabetic mice, diabetic mice treated with dapagliflozin displayed significantly lower arterial stiffness (Db = 469 cm/s vs. Db + dapa = 435 cm/s, p < 0.05), and improvements in endothelial dysfunction (area under the curve AUC Db = 57.2 vs. Db + dapa = 117.0, p < 0.05) and vascular smooth muscle dysfunction (AUC, Db = 201.7 vs. Db + dapa = 285.5, p < 0.05). These vascular improvements were accompanied by reductions in hyperglycemia and circulating markers of inflammation. The microbiota of Db and Con mice were distinctly different, and dapagliflozin treatment was associated with minor alterations in gut microbiota composition, particularly in Db mice, although these effects did not conclusively mediate the improvements in vascular function.
Dapagliflozin treatment improves arterial stiffness, endothelial dysfunction and vascular smooth muscle dysfunction, and subtly alters microbiota composition in type 2 diabetic mice. Collectively, the improvements in generalized vascular function may represent an important mechanism underlying the cardiovascular benefits of SGLT2i treatment.
Humans depend on our commensal bacteria for nutritive, immune-modulating, and metabolic contributions to maintenance of health. However, this commensal community exists in careful balance that, if ...disrupted, enters dysbiosis; this has been shown to contribute to the pathogenesis of colon, gastric, esophageal, pancreatic, laryngeal, breast, and gallbladder carcinomas. This development is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis and increases vulnerability to pathogens. Advances in sequencing technology have increased our ability to catalog microbial species associated with various cancer types across the body. However, defining microbial biomarkers as cancer predictors presents multiple challenges, and existing studies identifying cancer-associated bacteria have reported inconsistent outcomes. Combining metabolites and microbiome analyses can help elucidate interactions between gut microbiota, metabolism, and the host. Ultimately, understanding how gut dysbiosis impacts host response and inflammation will be critical to creating an accurate picture of the role of the microbiome in cancer.
Background The need to enhance the sustainability of intensive agricultural systems is widely recognized One promising approach is to encourage beneficial services provided by soil microorganisms to ...decrease the inputs of fertilizers and pesticides. However, limited success of this approach in field applications raises questions as to how this might be best accomplished. Scope We highlight connections between root exudates and the rhizosphere microbiome, and discuss the possibility of using plant exudation characteristics to selectively enhance beneficial microbial activities and microbiome characteristics. Gaps in our understanding and areas of research that are vital to our ability to more fully exploit the soil microbiome for agroecosystem productivity and sustainability are also discussed. Conclusion This article outlines strategies for more effectively exploiting beneficial microbial services on agricultural systems, and calls attention to topics that require additional research.
According to recent estimates, over one third of the human population will be diagnosed with cancer at some point in their lifetime. While genetic factors play a large part in cancer risk, as much as ...50 % of cancers may be preventable through various lifestyle modifications. Nutrition is a major modifiable risk factor, both through its impacts on obesity as well as through dietary chemical exposures that can either increase or decrease cancer risk. However, specific associations and mechanistic links between diet and cancer risk are either inconsistent or elusive. New insights regarding the reciprocal interactions between diet and the gut microbiota, the trillions of organisms that reside in our intestines, may help clarify how diet impacts cancer. The gut microbiota is largely shaped by an individual’s diet and has far-reaching effects on metabolism, the immune system, and inflammation- important factors in the development and progression of various cancers. Likewise, the microbiota modifies dietary components, and consequently, exposure to metabolites that can influence cancer. This review explores some of these diet-microbiota interactions in the context of their potential impacts on cancer prevention.
The gut microbiota is increasingly recognized as an important modulator of human health. As such, there is a growing need to identify effective means of selectively modifying gut microbial ...communities. Bacteriophages, which were briefly utilized as clinical antimicrobials in the early 20th century, present an opportunity to selectively reduce populations of undesirable microorganisms. However, whether intentional consumption of specific bacteriophages affects overall gut ecology is not yet known. Using a commercial cocktail of
-targeting bacteriophages, we examined their effects on gut microbiota and markers of intestinal and systemic inflammation in a healthy human population. In a double-blinded, placebo-controlled crossover trial, normal to overweight adults consumed bacteriophages for 28 days. Stool and blood samples were collected and used to examine inflammatory markers, lipid metabolism, and gut microbiota. Reductions in fecal
loads were observed with phage consumption. However, there were no significant changes to alpha and beta diversity parameters, suggesting that consumed phages did not globally disrupt the microbiota. However, specific populations were altered in response to treatment, including increases in members of the butyrate-producing genera
and a decreased proportion of taxa most closely related to
. Short-chain fatty acid production, inflammatory markers, and lipid metabolism were largely unaltered, but there was a small but significant decrease in circulating interleukin-4 (Il-4). Together, these data demonstrate the potential of bacteriophages to selectively reduce target organisms without global disruption of the gut community.
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