Nutrition-related predictors of complications and length of hospital stay following total pelvic exenteration surgery.

BACKGROUND & AIMS: Pelvic exenteration (PE) surgery is now a widely accepted procedure that is increasingly being performed worldwide but has significant morbidity. Although nutrition status, body mass index (BMI) and postoperative nutrition support practices are modifiable risk factors, few studies have examined the relationship of these with clinical outcomes following PE. The aim of this study was therefore to investigate the impact of these factors on postoperative complications and length of hospital stay (LOHS) following PE. METHODS: This was a retrospective cohort study of all patients having total PE surgery at a tertiary teaching hospital from 2012 to 2021 (n = 69). Multivariable analyses were undertaken to confirm univariate associations and adjust for confounding variables. Binary logistic regression was undertaken to explore predictors of infectious and Grade III or above Clavien-Dindo complications, and negative binomial regression to identify predictors of LOHS. RESULTS: Patients who were malnourished according to the Subjective Global Assessment were 5.66 (OR 5.66, 95% CI 1.07-29.74, p = 0.041) times more likely to develop an infectious complication. Increasing BMI was independently associated with development of Grade III or above Clavien-Dindo complications (p = 0.040). For each additional day until full diet commencement, there was a 19% (OR: 1.19, 95% CI 1.05-1.34, p = 0.005) increased incidence of significant complications and a 5.6% (IRR: 1.056, 95% CI: 1.02-1.09, p = 0.002) longer LOHS on multivariable analysis. There was a high rate of prolonged postoperative ileus (78%). The implementation of a nutrition support pathway with routine postoperative parenteral nutrition (PN) resulted in patients achieving adequate nutrition 7 days faster (p < 0.001) with minimal line-related complications (1.4% line-related thrombus). Routine PN did not impact ileus rates (p = 0.33) or time to diet commencement (p = 0.6). CONCLUSIONS: Preoperative malnutrition and higher BMI were associated with complications following PE. Delay to full diet commencement was associated with increased complications and longer LOHS. Routine postoperative PN appears safe and resulted in patients achieving adequate nutrition faster.

Changes in energy expenditure and physical activity over 15 years of environmental changes: The Maycoba project.

OBJECTIVE: This work aimed to parse out the role of changing environments on body composition, total energy expenditure, and physical activity in the Mexican Pima, a population experiencing rapid industrialization. METHODS: Using doubly labeled water, we compared energy expenditure and physical activity in a longitudinal cohort of Mexican Pima (n = 26; female: 12) in 1995 and 2010. Body mass and composition were assessed by bioimpedance analysis. To determine the effects of environmental factors on body weight independent of age, we compared the 1995 longitudinal cohort with an age- and sex-matched cross-sectional cohort (n = 26) in 2010. RESULTS: Body mass, fat mass, and fat-free mass all significantly increased between 1995 and 2010. Despite a 13% average increase in body weight, weight-adjusted total daily energy expenditure decreased significantly. Measured physical activity levels also decreased between 1995 and 2010, after we adjusted for weight. CONCLUSIONS: Our results suggest that the recent industrialization of the Maycoba region in Sonora, Mexico, has contributed to a decrease in physical activity, in turn contributing to weight gain and metabolic disease among the Mexican Pima.

Anatomically realistic aortic dissection simulator as a potential training tool for point-of-care ultrasound.

Aim: Simulators for aortic dissection diagnosis are limited by complex anatomy influencing the accuracy of point-of-care ultrasound for diagnosing aortic dissection. Therefore, this study aimed to create a healthy ascending aorta and class DeBakey, type II aortic dissection simulator as a potential point-of-care ultrasound training model. Material and methods: 3D mould simulators were created based on computed tomography images of one healthy and one DeBakey type II aortic dissection patient. In the next step, two polyvinyl alcohol-based and two silicone-based simulators were synthesised. Results: The results of the scanning electron microscope assessment showed an aortic dissection simulator's surface with disorganised surface texture and higher root mean square (RMS or Rq) value than the healthy model of polyvinyl alcohol (RqAD = 20.28 > RqAAo = 10.26) and silicone (RqAD = 33.8 > RqAAo = 23.07). The ultrasound assessment of diameter aortic dissection showed higher than the healthy ascending aorta in polyvinyl alcohol (dAD = 28.2 mm > dAAo = 20.2 mm) and Si (dAD = 31.0 mm > dAAo = 22.4 mm), while the wall thickness of aortic dissection showed thinner than the healthy aorta in polyvinyl alcohol, which is comparable with the actual aorta measurement. The intimal flap of aortic dissection was able to replicate and showed a false lumen in the ultrasound images. The flap was measured quantitatively, indicating that the intimal flap was hyperechoic. Conclusions: The simulators were able to replicate the surface morphology and echogenicity of the intimal flap, which is a linear hyperechoic area representing the separation of the aorta wall.

Impulse control and related behavioral disorders (ICRD) in Idiopathic Parkinson's Disease treated with different dopamine agonists in Hong Kong: Is any dopamine agonist better?

Objective: To assess the incidence of Impulse control and related behavioral disorders (ICRD) in Chinese Idiopathic Parkinson Disease (IPD) patients treated with different dopamine agonists (DA), and their clinical characteristics and associated risk factors. Methods: This was an observational cohort study based on clinical interviews and medical records of IPD patients treated with DA for >6 months in three hospitals in Hong Kong. The short version of Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP-S) was used to screen for ICRD. ICRD incidence among different DA, clinical characteristics and risk factors were examined. Results: Incidence of ICRD was analyzed in 311 patients taking their first, single DA. 43 patients (13.8 %) developed ICRD. The mean duration of IPD was 8.5 ± 5.6 years and median HY stage was 2.5. Bromocriptine and rotigotine users had lower ICRD incidence rate. Both pramipexole [adjusted HR 7.28 (2.46-21.54), p < 0.001] and ropinirole [adjusted HR 6.53 (2.67-15.99), p < 0.001] were independently associated with higher risk of ICRD compared to bromocriptine in multivariate analysis. Similarly, pramipexole and ropinirole appeared to carry higher risk compared to rotigotine but did not reach statistical significance. Male [adjusted HR 2.24 (1.07-4.72), p = 0.033], younger IPD onset [adjusted HR 2.99 (1.44-6.19) for onset < 50 year, p = 0.003] and history of psychiatric disorders [adjusted HR 2.80 (1.39-5.62), p = 0.004] were other independent risk factors. Conclusion: Bromocriptine and probably rotigotine carried a lower ICRD risk compared to pramipexole and ropinirole.

Food provision in Australian aged care homes does not meet protein needs of residents: A call for reform.

AIM: Malnutrition is common in older adults in aged care homes, partly due to inadequate protein intake. Menu planning guidelines are available however, adherence to guidelines is unknown. This study aimed to determine; (i) what are the average serving sizes of menu items provided and do they meet recommended portion sizes? (ii) does consumption from a 'typical' menu provide sufficient protein? and (iii) can substituting a 'typical' menu with high-protein options enable residents to achieve protein adequacy? METHODS: This study involved 572 residents (73% female; aged 86.4 ± 7.3 years) from 60 aged-care homes in Australia involved in a 2-year cluster-randomised trial. During the trial, food intake was recorded quarterly using visual estimation of plate-waste and 42 061 foods analysed. As part of a secondary analysis of these data, portion sizes of foods were compared to guidelines by calculating the mean (95% confidence interval). Items were deemed inadequate if the upper 95% confidence interval remained below recommended portion sizes. RESULTS: On average 47% of breakfast and 80% of lunch/dinner items were below recommended portion sizes. Relative protein intakes, from a typical menu (most consumed foods), was 0.9 g and 0.8 g/kg body weight/day for females and males; both below recommendations. Substituting regular items with higher protein equivalents increased protein intake to 1.3 g and 1.2 g/kg body weight/day, for females and males, respectively. CONCLUSION: Aged care homes in Australia are not meeting menu planning guidelines resulting in insufficient protein being provided. Reform to menu guidelines including provision of high-protein foods, will ensure protein adequacy in older adults in aged-care homes.

Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome.

The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.

Hypertrophic chondrocytes at the junction of musculoskeletal structures.

Hypertrophic chondrocytes are found at unique locations at the junction of skeletal tissues, cartilage growth plate, articular cartilage, enthesis and intervertebral discs. Their role in the skeleton is best understood in the process of endochondral ossification in development and bone fracture healing. Chondrocyte hypertrophy occurs in degenerative conditions such as osteoarthritis. Thus, the role of hypertrophic chondrocytes in skeletal biology and pathology is context dependent. This review will focus on hypertrophic chondrocytes in endochondral ossification, in which they exist in a transient state, but acting as a central regulator of differentiation, mineralization, vascularization and conversion to bone. The amazing journey of a chondrocyte from being entrapped in the extracellular matrix environment to becoming proliferative then hypertrophic will be discussed. Recent studies on the dynamic changes and plasticity of hypertrophic chondrocytes have provided new insights into how we view these cells, not as terminally differentiated but as cells that can dedifferentiate to more progenitor-like cells in a transition to osteoblasts and adipocytes, as well as a source of skeletal stem and progenitor cells residing in the bone marrow. This will provide a foundation for studies of hypertrophic chondrocytes at other skeletal sites in development, tissue maintenance, pathology and therapy.

Basilar artery diameter as neuroimaging biomarker in Chinese Fabry disease patients.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disease resulting from mutations of α-galactosidase A gene, and has been emphasized as one of the etiologies of young stroke and leukoencephalopathy. Vertebrobasilar dolichoectasia (VBD) is a highlighted finding in FD. We aim to examine the utility of VBD in Chinese FD by comparing the differences in basilar artery (BA) diameter of Chinese FD patients against age-matched controls with and without stroke. METHODS: This was a matched case-control study involving 37 Chinese FD patients. The BA diameters were evaluated on axial T2-weighted magnetic resonance imaging and compared to two age-and-gender matched control groups, one with stroke and one without. The association between BA diameter and stroke occurrences and white matter hyperintensities (WMH) were analyzed among all FD patients. RESULTS: Patients with FD had significantly increased BA diameter compared to controls with and without stroke (p < 0.001). A BA diameter of 4.16 mm could distinguish FD from controls in the stroke subgroup (ROC AUC 0.870, p = 0.001, sensitivity 80% specificity 100%), and with a cut-off of 3.21 mm in the non-stroke subgroup (ROC AUC 0.846, p < 0.001, sensitivity 77.8% specificity 88.9%). Larger BA diameter had more stroke occurrences and was moderately associated with heavier WMH load in terms of higher total FAZEKAS scores. (Spearman's rho = 0.423, p = 0.011). CONCLUSION: VBD was also present in Chinese FD patients. BA diameter has high diagnostic utility in identifying FD from a mixed cohort of stroke and normal controls, and carried predictive value in evaluating neurological complications of FD.

Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis.

Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R. gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R. gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R. gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.

Adapting and pretesting the World Health Organization's Caregiver Skills Training Program for children with autism and developmental disorders or delays in Hong Kong.

The World Health Organization Caregiver Skills Training Program (WHO-CST) was developed to strengthen caregivers' skills in supporting children with developmental delays and the caregivers' well-being. The WHO-CST Hong Kong (HK) was adapted, and pre-pilot tested to support families with children suspected of having developmental delays and autism spectrum disorder and to empower the caregivers to foster their children's learning, social communication, and adaptive behavior. A sequential mixed-methods research methodology was undertaken to examine the adaptation process and initial implementation experiences. The acceptability, feasibility, and perceived benefits of the WHO-CST were assessed using stakeholders' and caregivers' qualitative and caregivers' quantitative pre- and post-intervention feedback. The data included materials generated from (1) three consultation meetings with stakeholders; (2) detailed reviews of the translated and adapted WHO-CST materials by master trainees (n = 10) trained by the WHO-CST representatives; (3) needs assessment focus group interviews with caregivers (n = 15) of children with autism spectrum disorder; and (4) pre- and post-CST program qualitative focus group interviews and quantitative evaluation. Consultation with stakeholders suggested that the program was acceptable for the local community, but the home visit and fidelity components were initially considered to be challenges towards the feasibility and sustainability of the program. Caregivers in the needs assessment focus groups gave widely diverse views about the program's uniqueness, length, delivery mode, and the inclusion of videotaping in-home visits. Post-intervention comments by caregivers about the program were mainly positive, while the MTs were critical of the content and length of the training and fidelity process. As one of the first high-income locations to adopt the WHO-CST, the evaluation findings of the WHO-CST-HK indicate that it is feasible and acceptable to implement the program in a metropolitan area where families have busy work schedules and are very conscious of privacy issues. The study results suggest that the WHO-CST program in HK and other high-income countries require scaling up and further evaluation of its implementation in real community settings. This involves systemic and contextual changes to allow task-sharing between professionals and non-specialists at the macro level. Furthermore, technology should be used to support the supervision of non-specialists. In addition, easier access to the WHO-CST materials at the micro level is required to ensure equity, equality, diversity, and inclusion of diversified families of children with developmental delays.

Gut Microbiota and Phenotypic Changes Induced by Ablation of Liver- and Intestinal-Type Fatty Acid-Binding Proteins.

Intestinal fatty acid-binding protein (IFABP; FABP2) and liver fatty acid-binding protein (LFABP; FABP1) are small intracellular lipid-binding proteins. Deficiency of either of these proteins in mice leads to differential changes in intestinal lipid transport and metabolism, and to markedly divergent changes in whole-body energy homeostasis. The gut microbiota has been reported to play a pivotal role in metabolic process in the host and can be affected by host genetic factors. Here, we examined the phenotypes of wild-type (WT), LFABP-/-, and IFABP-/- mice before and after high-fat diet (HFD) feeding and applied 16S rRNA gene V4 sequencing to explore guild-level changes in the gut microbiota and their associations with the phenotypes. The results show that, compared with WT and IFABP-/- mice, LFABP-/- mice gained more weight, had longer intestinal transit time, less fecal output, and more guilds containing bacteria associated with obesity, such as members in family Desulfovibrionaceae. By contrast, IFABP-/- mice gained the least weight, had the shortest intestinal transit time, the most fecal output, and the highest abundance of potentially beneficial guilds such as those including members from Akkermansia, Lactobacillus, and Bifidobacterium. Twelve out of the eighteen genotype-related bacterial guilds were associated with body weight. Interestingly, compared with WT mice, the levels of short-chain fatty acids in feces were significantly higher in LFABP-/- and IFABP-/- mice under both diets. Collectively, these studies show that the ablation of LFABP or IFABP induced marked changes in the gut microbiota, and these were associated with HFD-induced phenotypic changes in these mice.

A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection.

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for γδ IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the γδ IEL compartment under homeostatic conditions has yet to be determined. We identified a novel γδ IEL hyperproliferative phenotype that arises early in life and is characterized by expansion of multiple Vγ subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal γδ IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in γδ IELs. Further, we identified two guilds of small intestinal or fecal bacteria represented by 12 amplicon sequence variants (ASV) that are strongly associated with γδ IEL expansion. Using intravital microscopy, we find that hyperproliferative γδ IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate γδ IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier.

Daily Exposure to a Cranberry Polyphenol Oral Rinse Alters the Oral Microbiome but Not Taste Perception in PROP Taster Status Classified Individuals.

Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline (p = 0.012) but not after the intervention (p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs (p = 0.023) but not in STs (p = 0.096). The intervention also altered specific salivary protein levels (α-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.

Therapeutic effects and mechanisms of Zhen-Wu-Bu-Qi Decoction on dextran sulfate sodium-induced chronic colitis in mice assessed by multi-omics approaches.

BACKGROUND: Zhen-Wu-Bu-Qi Decoction (ZWBQD), a traditional Chinese medicine formula comprising Poria, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Rhizoma Zingiberis Recens, Radix Codonopsis and Rhizoma Coptidis, is used for treating ulcerative colitis (UC). In a previous study, we have reported ZWBQD mitigates the severity of dextran sulfate sodium (DSS)-induced colitis in mice. HYPOTHESIS: In this study, we aimed to understand the systemic actions and underlying mechanisms of ZWBQD on experimental colitis in mice. METHODS: We used multi-omics techniques and immunoblotting approach to study the pharmacological actions and mechanisms of ZWBQD in DSS-induced chronic colitic mice. RESULTS: We showed that ZWBQD exhibited potent anti-inflammatory properties and significantly protected DSS-induced colitic mice against colon injury by regulating the PI3K-AKT, MAPK signaling pathway and NF-κB signaling pathways. We also revealed that ZWBQD significantly ameliorated gut microbiota dysbiosis and abnormalities of tryptophan catabolites induced by DSS. CONCLUSIONS: We demonstrated that the therapeutic effects of ZWBQD on experimental colitis are mediated by regulating multiple signaling pathways and modulation of gut microbiota. Our study employed an integrative strategy to elucidate novel mechanisms of ZWBQD, which provides new insights into the development of Chinese herbal medicine-based therapeutics for UC.

Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes.

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.

Demographic and Epidemiological Contributions to Recent Trends in Cancer Incidence in Hong Kong.

BACKGROUND: Hong Kong has an ageing Chinese population with high life expectancy and a rising number of cancer cases. While population ageing could lead to higher incidence, we aim to quantify the demographic and epidemiological contributions to this trend by disentangling the effect of these factors. METHODS: We analysed secular trends of cancer incidences of all cancer sites combined, including the five top cancers in men and women in Hong Kong in 1983-2017, by disentangling effects of demographics (ageing population and population growth) and cancer risk/rate change using the RiskDiff methodology. RESULTS: Overall, age-standardised incidences of all cancers combined in women and in men declined over the study period (-5.3% for women, -30.2% for men), but total incident cancer case counts increased dramatically (156.5% for women, 96% for men). This increase was primarily due to ageing and increasing population (95% age, 66.1% growth for women, and 119.4% age, 25.4% growth for men), while disease risk for all cancers combined has a decreasing trend (-4.5% for women and -48.8% for men). For the site-specific risk changes among the most five common cancer types, there were increases in risks of prostate and colorectal cancers in men, and breast, endometrial, and thyroid cancers in women. CONCLUSION: Demographic changes and ageing in our Chinese population resulted in a marked increase in the number of cancer diagnoses in Hong Kong in past decades. The surge in incident case counts overall is expected to stress the healthcare system in terms of the increased demand of healthcare professionals. Cancer surveillance should be enhanced in view of the growing demand from older patients and the cancer types with fast-increasing incidence rates in our population.

The Effects of Green Tea on Diabetes and Gut Microbiome in db/db Mice: Studies with Tea Extracts vs. Tea Powder.

Green tea extracts and tea catechins have been shown to prevent or alleviate diabetes. The present study tests the hypothesis that green tea leaves in powder form (GTP), which also contain fiber and other water non-extractable materials, are more effective than the corresponding green tea extracts (GTE) in impeding the development of diabetes in db/db mice. Female db/db mice were treated with a diet containing 1% of GTE, 2% of GTE, 2% of GTP (with the same catechin content as 1% GTE) or 1% GTP. The 1% GTE group had lower food intake, water consumption, body weight and fasting blood glucose levels than the control group, while 2% GTP did not have any significant effect. Dietary 1% GTE also preserved ß-cell insulin secretion. However, 1% GTP increased food intake, water consumption and blood glucose levels. Microbiome analysis with 16S rRNA gene V4 sequencing showed that the gut microbiota was modified by GTE and GTP, and a few bacterial guilds were associated with blood glucose levels. In the Random Forest regression model, the leading predictor of metabolic outcome was food consumption, followed by changes in some bacterial guilds. The results illustrate the importance of food consumption and gut microbiota in affecting the progression of diabetes.

Elemental iron modifies the redox environment of the gastrointestinal tract: A novel therapeutic target and test for metabolic syndrome.

Metabolic syndrome (MetS, i.e., type 2 diabetes and obesity) is often associated with dysbiosis, inflammation, and leaky gut syndrome, which increase the content of oxygen and reactive oxygen species (ROS) in the gastrointestinal (GI) tract. Using near-infrared fluorescent, in situ imaging of ROS, we evaluated the effects of oral administration of elemental iron powder (Fe0) on luminal ROS in the GI tract and related these changes to glucose metabolism and the gut microbiome. C57Bl/6J mice fed low-fat or high-fat diets and gavaged with Fe0 (2.5 g per kg), in both single- and repeat-doses, demonstrated decreased levels of luminal ROS. Fourteen days of repeated Fe0 administration reduced hyperglycemia and improved glucose tolerance in the obese and hyperglycemic animals compared to the untreated obese controls and reduced the relative amount of iron oxides in the feces, which indicated an increased redox environment of the GI tract. We determined that Fe0 administration can also be used as a diagnostic assay to assess the GI microenvironment. Improved metabolic outcomes and decreased gastrointestinal ROS in Fe0-treated, high-fat diet-fed animals correlated with the increase in a co-abundance group of beneficial bacteria, including Lactobacillus, and the suppression of detrimental populations, including Oscillibacter, Peptococcus, and Intestinimonas. Daily Fe0 treatment also increased the relative abundance of amplicon sequence variants that lacked functional enzymatic antioxidant systems, which is consistent with the ability of Fe0 to scavenge ROS and oxygen in the GI, thus favoring the growth of oxygen-sensitive bacteria. These findings delineate a functional role for antioxidants in modification of the GI microenvironment and subsequent reversal of metabolic dysfunction.

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome.

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.

Guild-based analysis for understanding gut microbiome in human health and diseases.

To demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem's higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same "guild" if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of "guild" to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.