Purified diets containing high levels of soluble fiber and grain-based diets promote similar gastrointestinal morphometry yet distinct microbial communities.

Dietary fibers play a crucial role in shaping the gut microbiome and influencing gastrointestinal (GI) physiology. Grain-based diets (GBDs) are widely used in rodent studies, but their utility is limited due to batch-to-batch variability resulting from inconsistent ingredients. Purified diets (PDs) are composed of only known and refined ingredients and offer a solution to the constraints of GBDs. This study aimed to identify a combination of dietary fibers in a purified diet (PD) that promotes optimal murine gut morphometry and a diverse intestinal microbial community. Male C57BL/6J mice were fed either two grain-based diets (GBDs) or four PDs with varying fiber compositions for 28 days. Mice consuming PDs lacking soluble fiber had more gonadal fat (P < 0.05), shorter small intestines (P < 0.05), and lighter ceca (P < 0.05) compared with those fed the LabDiet 5001 GBD. Increasing the proportion of soluble fibers in PDs progressively reduced microbial diversity in the cecum and colon. Multidimensional scaling analysis revealed distinct microbial communities in the cecum and colon between mice fed GBDs and PDs (P < 0.05). Differential abundance analysis identified relatively more Family XII UCG 001 and less Lactococcus in mice fed GBDs relative to mice consuming PDs (P < 0.05). While no PD recapitulated the gut microbial composition of GBDs, PDs with high soluble fiber content best preserved GI morphometry. These findings underscore the importance of considering diet as an experimental variable and highlight the need for a PD formulation that combines the benefits of GBDs on GI health and microbial richness. IMPORTANCE: Dietary fibers are essential for maintaining gut health. Insoluble fibers aid in fecal bulking and water retention while soluble fiber is a fermentative substrate for intestinal microbial communities. Grain-based diets (GBDs) are commonly used in preclinical research but the variability in ingredients across batches impedes reproducibility. Purified diets (PDs), which are composed of highly refined ingredients, pose a potential solution but the most widely used low-fat control PDs contain no soluble fiber. This study intended to identify a PD with a combination of fibers that promotes murine gut health and microbial diversity. A PD with optimal fiber composition would aid in the standardization and reproducibility of studies investigating intestinal physiology and the gut microbiota.

Intestinal Energy Harvest Mediates Gut Microbiota-Associated Weight Loss Following Bariatric Surgery.

PURPOSE: Metabolic and bariatric surgery (MBS) is the most effective treatment for class III obesity. The capacity to efficiently extract intestinal energy is potentially a determinant of varying weight loss outcomes post-MBS. Prior research indicated that intestinal energy harvest is correlated with post-MBS weight loss. Studies have also demonstrated that the gut microbiota is associated with weight loss post-MBS. We aim to investigate whether gut microbiota-associated weight loss is mediated by intestinal energy harvest in patients post-MBS. MATERIALS AND METHODS: We examined the relationship between specific gut microbiota, intestinal energy harvest, diet, and weight loss using fecal metagenomic sequence data, bomb calorimetry (fecal energy content as a proxy for calorie absorption), and a validated dietary questionnaire on 67 individuals before and after MBS. Mediation analysis and a machine learning algorithm were conducted. RESULTS: Intestinal energy harvest was a mediator in the relationship between the intestinal microbiota (Bacteroides caccae) and weight loss outcomes in patients post-MBS at 18 months (M). The association between the abundance of B. caccae and post-MBS weight loss rate at 18 M was partly mediated by 1 M intestinal energy harvest (ß = 0.001 ± 0.001, P = 0.020). This mediation represents 2.83% of the total effect (ß = 0.050 ± 0.047; P = 0.028). Intestinal microbiota and energy harvest improved random forest model's accuracy in predicting weight loss results. CONCLUSION: Energy harvest partly mediates the relationship between the intestinal microbiota and weight loss outcomes among patients post-MBS. This study elucidates a potential mechanism regarding how intestinal energy absorption facilitates the effect of intestinal microbiota on energy metabolism and weight loss outcomes.

Energy expenditure during nutritional rehabilitation: a scoping review to investigate hypermetabolism in individuals with anorexia nervosa.

BACKGROUND: Weight gain and nutritional rehabilitation are essential first steps to achieve medical stabilization in anorexia nervosa, and frequent resistance to weight gain requires patients to consume high kilocalorie loads. Adaptive hypometabolism is common when patients begin treatment, and rebound hypermetabolism is suspected to be a significant barrier to weight gain. The aim of this review was to summarize existing data describing metabolic changes in anorexia nervosa during weight restoration. The reported findings challenge current hypotheses of weight gain resistance and highlight key areas for future research. METHODS: Using scoping review guidelines, three databases were searched for studies investigating metabolic changes in anorexia nervosa before and after renourishment. Two reviewers systematically screened the titles and abstracts of 447 articles, and full-text versions of 106 studies were assessed for eligibility. A total of 36 studies were included for review. Data regarding the study description, sample population (including age, weight, BMI, duration of treatment, and caloric intake), and metabolic variable descriptions were extracted. RESULTS: Female patients with anorexia nervosa from studies across 13 countries were included. Across the studies, average BMI increased from 13.7 kg/m2 at admission to 17.57 kg/m2. Patients presented to treatment with clinically reduced energy expenditure levels. After varying levels of nutritional rehabilitation and weight restoration, measured energy expenditure increased significantly in 76% of the studies. Energy expenditure values at the second timepoint increased to the standard range for normal weight female teenagers and adults. Despite these increases, the studies do not indicate the presence of a hypermetabolic state during renourishment. Additionally, all studies including both measured and predicted energy expenditure reported that predicted energy expenditure overestimated measured values. CONCLUSION: This study provides a detailed evaluation of the literature investigating energy expenditure and metabolic rate in patients with anorexia nervosa before and following a period of renourishment. The findings from this review identify important gaps in the current beliefs of energy expenditure in anorexia nervosa and highlight a need for further exploration of metabolic alterations during weight restoration.

Nutritional rehabilitation and weight restoration are two primary goals of anorexia nervosa treatment that pose significant physiological and psychological challenges for patients. Patients often require high caloric loads to continue an adequate weight gain trajectory, but the underlying cause of weight gain resistance remains unknown. We completed a scoping review of research into energy expenditure and metabolic rate during treatment. Our search identified 447 relevant articles from academic databases, and 106 were deemed eligible after screening. We extracted data, including sample characteristics, kilocalorie intake, energy expenditure, and treatment information, from 36 studies. When individuals arrived for treatment, their energy expenditure was lower than that of individuals without an eating disorder due to the prolonged state of nutrient deprivation. After varying amounts of time and kilocalorie intake, most studies reported significant increases in energy expenditure. However, energy expenditure after a period of renourishment did not indicate an overactive metabolism (i.e., "hypermetabolism"). Funders should consider supporting exploration of additional factors that may be functioning as barriers to weight gain during treatment, in pursuit of making treatment more efficient and long-lasting. Additionally, future research describing metabolism in anorexia nervosa should provide more consistent methodologies, robust statical testing, and comprehensive reporting of dietary intake.

Gut microbiota are differentially correlated with blood pressure status in African American collegiate athletes: A pilot study.

Hypertension (HTN) is common among athletes and the most recent epidemiologic data reports that cardiovascular (CV) sudden death is significantly greater in African Americans (AAs). Gut microbial dysbiosis (a poorly diverse stool microbial profile) has been associated with HTN in sedentary people but microbial characteristics of athletes with HTN are unknown. Our purpose was to differentiate microbiome characteristics associated with BP status in AA collegiate athletes. Thirty AA collegiate athletes were stratified by normal BP (systolic BP (SBP) ≤130 mmHg; n = 15) and HTN (SBP ≥130 mmHg; n = 15). 16S rRNA gene sequencing was performed on stool samples to identify microbes at the genus level. We did not observe any significant differences in alpha diversity, but beta diversity was different between groups. Principal coordinate analysis was significantly different (PERMANOVA, p < 0.05, R = 0.235) between groups. Spearman rank correlations showed a significant (p < 0.05) correlation between systolic BP and abundances for Adlercreutzia (R = 0.64), Coprococcus (R = 0.49), Granulicatella (R = 0.63), and Veillonella (R = 0.41). Gut microbial characteristics were associated with differentially abundant microbial genus' and BP status. These results will direct future studies to define the functions of these microbes associated with BP in athletes.

Giardia Antagonizes Beneficial Functions of Indigenous and Therapeutic Intestinal Bacteria during Malnutrition.

Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp . and an increase in Bifidobacterium spp . This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp . mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia , despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.

Eating disorders: are gut microbiota to blame?

Gut microbiota could be involved in weight regulation and impact brain function via the gut-brain axis. Moreover, gut microbiota may impact the development of eating disorders (EDs) since they are characterized by weight-related concerns and symptoms and may represent a therapeutic target if future research can establish a causal link.

A consortia of clinical E. coli strains with distinct in vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.

BACKGROUND: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. RESULTS: Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. CONCLUSIONS: Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.

Calorie restriction outperforms bariatric surgery in a murine model of obesity and triple-negative breast cancer.

Obesity promotes triple-negative breast cancer (TNBC), and effective interventions are urgently needed to break the obesity-TNBC link. Epidemiologic studies indicate that bariatric surgery reduces TNBC risk, while evidence is limited or conflicted for weight loss via low-fat diet (LFD) or calorie restriction (CR). Using a murine model of obesity-driven TNBC, we compared the antitumor effects of vertical sleeve gastrectomy (VSG) with LFD, chronic CR, and intermittent CR. Each intervention generated weight and fat loss and suppressed tumor growth relative to obese mice (greatest suppression with CR). VSG and CR regimens exerted both similar and unique effects, as assessed using multiomics approaches, in reversing obesity-associated transcript, epigenetics, secretome, and microbiota changes and restoring antitumor immunity. Thus, in a murine model of TNBC, bariatric surgery and CR each reverse obesity-driven tumor growth via shared and distinct antitumor mechanisms, and CR is superior to VSG in reversing obesity's procancer effects.

Longer-Term Weight Loss Outcomes Are Not Primarily Driven by Diet Following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

Metabolic and bariatric surgery (MBS) is the most effective long-term treatment for Class III obesity. Reduced dietary intake is considered a behavioral driver of post-surgical weight loss, but limited data have examined this association. Therefore, this study examined prospective, longitudinal relationships between dietary intake and weight loss over 24 months following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy. Relationships between weight loss and dietary intake were examined using a validated 24-h dietary recall method. Associations between total energy/macronutrient intake and weight loss outcomes were assessed at 12-, 18-, and 24-months following MBS, defining patients as "responders" and "suboptimal responders". Consistent with previous literature, 12-month responders and suboptimal responders showed significant associations between weight loss and energy (p = 0.018), protein (p = 0.002), and total fat intake (p = 0.005). However, this study also revealed that many of these associations are no longer significant 24 months post-MBS (p > 0.05), despite consistent weight loss trends. This study suggests a short-term signal between these dietary factors and weight loss outcomes 12 months post-MBS; however, this signal does not persist beyond 12 months. These results are essential for interpreting and designing clinical studies measuring long-term post-surgical weight loss outcomes.

Gut Microbial Changes Following Fecal Microbiota Transplantation for D-Lactic Acidosis in Two Children.

D-lactic acidosis (D-LA) is an uncommon complication of short bowel syndrome characterized by elevated plasma D-lactate and encephalopathy. Treatments include rehydration, dietary carbohydrate restriction, and antibiotics to alter the gut microbiota. Fecal microbiota transplantation (FMT) has recently been used in children to successfully treat D-LA. We compared the clinical course and then utilized metagenomic shotgun sequencing to describe changes in the composition and function of the intestinal microbiome following FMT in 2 patients with recurrent D-LA. FMT altered the composition of the fecal microbiota in these 2 patients with recurrent D-LA, though not necessarily in a consistent manner. Importantly, microbial metabolic pathways were also impacted by FMT, which may be critical for achieving desired clinical outcomes. While sample size limits the generalizability of our results, these findings set the stage for further understanding of the role of microbes in the pathogenesis of recurrent D-LA.

Laxative Abuse Is Associated With a Depleted Gut Microbial Community Structure Among Women and Men With Binge-Eating Disorder or Bulimia Nervosa: The Binge Eating Genetics Initiative.

OBJECTIVE: This study assessed the associations of binge eating, compensatory behaviors, and dietary restraint with the composition and diversity of the intestinal microbiota among participants with binge-eating disorder or bulimia nervosa. METHODS: We analyzed data from 265 participants aged 18 to 45 years with current binge-eating disorder or bulimia nervosa enrolled in the Binge Eating Genetics Initiative study. We evaluated the associations of binge-eating frequency; presence/absence and frequency of vomiting, laxative use, and compulsive exercise; and dietary restraint with abundances of gut microbial genera, species, and diversity (Shannon diversity, Faith phylogenetic diversity, and Peilou's evenness) from 16S rRNA gene sequencing. General linear regression models adjusted for potential confounders, including age and current body mass index, were used to test associations; p values were corrected for the false discovery rate. RESULTS: The normalized abundance of four genus- and species-level gut microbes and three diversity indices were lower among Binge Eating Genetics Initiative participants who reported any laxative use compared with those who reported no laxative use. Vomiting frequency was positively associated with the normalized abundance of the genus Escherichia-Shigella , a potential pathobiont, although the association was attenuated to nonsignificance after adjustment for age, body mass index, and binge-eating episodes. CONCLUSIONS: Laxative use was highly and uniformly predictive of a reduced gut microbial diversity including potential commensals and pathobionts, and should be assessed and accounted for in all future studies of eating disorders and the gut microbiota. Future studies should collect data on specific medications-particularly laxatives-and dietary intake to obtain unbiased estimates of the effect of eating disorders on the gut microbiota and identify potential downstream clinical implications.Trial Registration:ClinicalTrials.gov identifier: NCT04162574 .

A consortia of clinical E. coli strains with distinct in-vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.

Background: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. Results: Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. Conclusions: Our findings establish the in-vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in-vivo colonization dynamics of patient-derived bacteria in murine models.

Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy.

Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children. Here we leverage the MAL-ED longitudinal birth cohort and a model of Giardia mono-association in gnotobiotic and immunodeficient mice to propose an alternative pathogenesis of this parasite. In children, Giardia results in linear growth deficits and gut permeability that are dose-dependent and independent of intestinal markers of inflammation. The estimates of these findings vary between children in different MAL-ED sites. In a representative site, where Giardia associates with growth restriction, infected children demonstrate broad amino acid deficiencies, and overproduction of specific phenolic acids, byproducts of intestinal bacterial amino acid metabolism. Gnotobiotic mice require specific nutritional and environmental conditions to recapitulate these findings, and immunodeficient mice confirm a pathway independent of chronic T/B cell inflammation. Taken together, we propose a new paradigm that Giardia-mediated growth faltering is contingent upon a convergence of this intestinal protozoa with nutritional and intestinal bacterial factors.

The microbiota-gut-brain axis and perceived stress in the perinatal period.

Perinatal perceived stress can contribute to worse health outcomes for the parent-child dyad. Given the emerging relationship between the microbiota-gut-brain axis and stress, this study sought to elucidate connections between bowel symptoms and the gut microbiome in relation to perceived stress at three time points in the perinatal period: two during pregnancy and one postpartum. Ninety-five pregnant individuals participated in a prospective cohort study from April 2017 to November 2019. Researchers assessed Perceived Stress Scale-10 (PSS); bowel symptoms (according to the IBS Questionnaire); psychiatrist assessment of new onset or exacerbated depression and anxiety; and fecal samples analyzed for alpha diversity (measures of gut microbiome diversity utilizing Shannon, Observed OTUs, and Faith's PD) at each timepoint. Covariates included weeks of gestation and weeks postpartum. PSS scores were divided into "Perceived Self-Efficacy" and "Perceived Helplessness." Increased gut microbial diversity was associated with decreased bowel symptoms, decreased overall perceived stress, increased ability to cope with adversity, and decreased distress in the postpartum period. This study found a significant association between a less diverse microbial community, lower self-efficacy early in pregnancy, and greater bowel symptoms and perceived helplessness later in the perinatal period, relationships that may ultimately point to novel diagnostic methods and interventions for perceived stress based on the microbiota-gut-brain axis.

Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity.

BACKGROUND: Diet, a key component of type 1 diabetes (T1D) management, modulates the intestinal microbiota and its metabolically active byproducts-including SCFA-through fermentation of dietary carbohydrates such as fiber. However, the diet-microbiome relationship remains largely unexplored in longstanding T1D. OBJECTIVES: We evaluated whether increased carbohydrate intake, including fiber, is associated with increased SCFA-producing gut microbes, SCFA, and intestinal microbial diversity among young adults with longstanding T1D and overweight or obesity. METHODS: Young adult men and women with T1D for ≥1 y, aged 19-30 y, and BMI of 27.0-39.9 kg/m2 at baseline provided stool samples at baseline and 3, 6, and 9 mo of a randomized dietary weight loss trial. Diet was assessed by 1-2 24-h recalls. The abundance of SCFA-producing microbes was measured using 16S rRNA gene sequencing. GC-MS measured fecal SCFA (acetate, butyrate, propionate, and total) concentrations. Adjusted and Bonferroni-corrected generalized estimating equations modeled associations of dietary fiber (total, soluble, and pectins) and carbohydrate (available carbohydrate, and fructose) with microbiome-related outcomes. Primary analyses were restricted to data collected before COVID-19 interruptions. RESULTS: Fiber (total and soluble) and carbohydrates (available and fructose) were positively associated with total SCFA and acetate concentrations (n = 40 participants, 52 visits). Each 10 g/d of total and soluble fiber intake was associated with an additional 8.8 µmol/g (95% CI: 4.5, 12.8 µmol/g; P = 0.006) and 24.0 µmol/g (95% CI: 12.9, 35.1 µmol/g; P = 0.003) of fecal acetate, respectively. Available carbohydrate intake was positively associated with SCFA producers Roseburia and Ruminococcus gnavus. All diet variables except pectin were inversely associated with normalized abundance of Bacteroides and Alistipes. Fructose was inversely associated with Akkermansia abundance. CONCLUSIONS: In young adults with longstanding T1D, fiber and carbohydrate intake were associated positively with fecal SCFA but had variable associations with SCFA-producing gut microbes. Controlled feeding studies should determine whether gut microbes and SCFA can be directly manipulated in T1D.

Interactions between perceived stress and microbial-host immune components: two demographically and geographically distinct pregnancy cohorts.

Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota, reflecting environment and social interactions, alongside host immune responses have the potential to better understand perceived stress and identify when stress is excessive in pregnancy. Two U.S. cohorts of 84 pregnant individuals, composed of urban women of color and suburban white women, completed the Perceived Stress Scale-10 (PSS-10) and provided fecal and blood samples at two time points. Confirmatory Factor Analysis assessed the robustness of a two-factor PSS-10 model (Emotional Distress/ED and Self-Efficacy/SE). Gut microbiota composition was measured by 16 S rRNA amplicon sequencing and the immune system activity was assessed with a panel of 21 T-cell related cytokines and chemokines. ED levels were higher in the suburban compared to the urban cohort, but levels of SE were similar. ED and SE levels were associated with distinct taxonomical signatures and the gut microbiota data improved the prediction of SE levels compared with models based on socio-demographic characteristics alone. Integration of self-reported symptoms, microbial and immune information revealed a possible mediation effect of Bacteroides uniformis between the immune system (through CXCL11) and SE. The study identified links between distinct taxonomical and immunological signatures with perceived stress. The data are congruent with a model where gut microbiome and immune factors, both impacting and reflecting factors such as close social relationships and dietary fiber, may modulate neural plasticity resulting in increased SE during pregnancy. The predictive value of these peripheral markers merit further study.

Associations of disordered eating with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes.

BACKGROUND AND AIMS: Disordered eating (DE) in type 1 diabetes (T1D) includes insulin restriction for weight loss with serious complications. Gut microbiota-derived short chain fatty acids (SCFA) may benefit host metabolism but are reduced in T1D. We evaluated the hypothesis that DE and insulin restriction were associated with reduced SCFA-producing gut microbes, SCFA, and intestinal microbial diversity in adults with T1D. METHODS AND RESULTS: We collected stool samples at four timepoints in a hypothesis-generating gut microbiome pilot study ancillary to a weight management pilot in young adults with T1D. 16S ribosomal RNA gene sequencing measured the normalized abundance of SCFA-producing intestinal microbes. Gas-chromatography mass-spectrometry measured SCFA (total, acetate, butyrate, and propionate). The Diabetes Eating Problem Survey-Revised (DEPS-R) assessed DE and insulin restriction. Covariate-adjusted and Bonferroni-corrected generalized estimating equations modeled the associations. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 data. Data were available for 45 participants at 109 visits, which included 42 participants at 65 visits pre-COVID-19. Participants reported restricting insulin "At least sometimes" at 53.3% of visits. Pre-COVID-19, each 5-point DEPS-R increase was associated with a -0.34 (95% CI -0.56, -0.13, p = 0.07) lower normalized abundance of genus Anaerostipes; and the normalized abundance of Lachnospira genus was -0.94 (95% CI -1.5, -0.42), p = 0.02 lower when insulin restriction was reported "At least sometimes" compared to "Rarely or Never". CONCLUSION: DE and insulin restriction were associated with a reduced abundance of SCFA-producing gut microbes pre-COVID-19. Additional studies are needed to confirm these associations to inform microbiota-based therapies in T1D.

Reproducible changes in the anorexia nervosa gut microbiota following inpatient therapy remain distinct from non-eating disorder controls.

The composition of the gut microbiota in patients with anorexia nervosa (AN), and the ability of this microbial community to influence the host, remains uncertain. To achieve a broader understanding of the role of the intestinal microbiota in patients with AN, we collected fecal samples before and following clinical treatment at two geographically distinct eating disorder units (Center of Excellence for Eating Disorders [UNC-CH] and ACUTE Center for Eating Disorders [Denver Health]). Gut microbiotas were characterized in patients with AN, before and after inpatient treatment, and in non-eating disorder (non-ED) controls using shotgun metagenomic sequencing. The impact of inpatient treatment on the AN gut microbiota was remarkably consistent between eating disorder units. Although weight in patients with AN showed improvements, AN microbiotas post-treatment remained distinct from non-ED controls. Additionally, AN gut microbiotas prior to treatment exhibited more fermentation pathways and a lower ability to degrade carbohydrates than non-ED controls. As the intestinal microbiota can influence nutrient metabolism, our data highlight the complex microbial communities in patients with AN as an element needing further attention post inpatient treatment. Additionally, this study defines the effects of renourishment on the AN gut microbiota and serves as a platform to develop precision nutrition approaches to potentially mitigate impediments to recovery.

The Intestinal Microbiota and Short-Chain Fatty Acids in Association with Advanced Metrics of Glycemia and Adiposity Among Young Adults with Type 1 Diabetes and Overweight or Obesity.

Background: Comanagement of glycemia and adiposity is the cornerstone of cardiometabolic risk reduction in type 1 diabetes (T1D), but targets are often not met. The intestinal microbiota and microbiota-derived short-chain fatty acids (SCFAs) influence glycemia and adiposity but have not been sufficiently investigated in longstanding T1D. Objectives: We evaluated the hypothesis that an increased abundance of SCFA-producing gut microbes, fecal SCFAs, and intestinal microbial diversity were associated with improved glycemia but increased adiposity in young adults with longstanding T1D. Methods: Participants provided stool samples at ≤4 time points (NCT03651622: https://clinicaltrials.gov/ct2/show/NCT03651622). Sequencing of the 16S ribosomal RNA gene measured abundances of SCFA-producing intestinal microbes. GC-MS measured total and specific SCFAs (acetate, butyrate, propionate). DXA (body fat percentage and percentage lean mass) and anthropometrics (BMI) measured adiposity. Continuous glucose monitoring [percentage of time in range (70-180 mg/dL), above range (>180 mg/dL), and below range (54-69 mg/dL)] and glycated hemoglobin (i.e., HbA1c) assessed glycemia. Adjusted and Bonferroni-corrected generalized estimating equations modeled the associations of SCFA-producing gut microbes, fecal SCFAs, and intestinal microbial diversity with glycemia and adiposity. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 visits. Results: Data were available for ≤45 participants at 101 visits (including 40 participants at 54 visits pre-COVID-19). Abundance of Eubacterium hallii was associated inversely with BMI (all data). Pre-COVID-19, increased fecal propionate was associated with increased percentage of time above range and reduced percentage of time in target and below range; and abundances of 3 SCFA-producing taxa (Ruminococcus gnavus, Eubacterium ventriosum, and Lachnospira) were associated inversely with body fat percentage, of which two microbes were positively associated with percentage lean mass. Abundance of Anaerostipes was associated with reduced percentage of time in range (all data) and with increased body fat percentage and reduced percentage lean mass (pre-COVID-19). Conclusions: Unexpectedly, fecal propionate was associated with detriment to glycemia, whereas most SCFA-producing intestinal microbes were associated with benefit to adiposity. Future studies should confirm these associations and determine their potential causal linkages in T1D.This study is registered at clinical.trials.gov (NCT03651622; https://clinicaltrials.gov/ct2/show/NCT03651622).

Association of Increased Serum Lipopolysaccharide, But Not Microbial Dysbiosis, With Obesity-Related Osteoarthritis.

OBJECTIVE: To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA). METHODS: Stool and blood samples were collected from 92 participants with a body mass index (BMI) ≥30 kg/m2 , recruited from the Johnston County Osteoarthritis Project. OA patients (n = 50) had hand and knee OA (Kellgren/Lawrence [K/L] grade ≥2 or arthroplasty). Controls (n = 42) had no hand OA and a K/L grade of 0-1 for the knees. Compositional analysis of stool samples was carried out by 16S ribosomal RNA amplicon sequencing. Alpha- and beta-diversity and differences in taxa relative abundances were determined. Blood samples were used for multiplex cytokine analysis and measures of lipopolysaccharide (LPS) and LPS binding protein. Germ-free mice were gavaged with patient- or control-pooled fecal samples and fed a 40% fat, high-sucrose diet for 40 weeks. Knee OA was evaluated histologically. RESULTS: On average, OA patients were slightly older than the controls, consisted of more women, and had a higher mean BMI, higher mean Western Ontario and McMaster Universities Osteoarthritis Index pain score, and higher mean K/L grade. There were no significant differences in α- or ß-diversity or genus level composition between patients and controls. Patients had higher plasma levels of osteopontin (P = 0.01) and serum LPS (P < 0.0001) compared to controls. Mice transplanted with patient or control microbiota exhibited a significant difference in α-diversity (P = 0.02) and ß-diversity, but no differences in OA severity were observed. CONCLUSION: The lack of differences in the gut microbiota, but increased serum LPS levels, suggest the possibility that increased intestinal permeability allowing for greater absorption of LPS, rather than a dysbiotic microbiota, may contribute to the development of OA associated with obesity.