Retail programs offer popular weight-loss options amid the ongoing obesity crisis. However, research on weight-loss outcomes within such programs is limited. This prospective-cohort observational study enrolled 58 men and women between ages 20 and 72 years from a retail program to assess the influence of client features on energy-restriction induced weight-loss response. DESeq2 in R-studio, a linear regression model adjusting for significantly correlating covariates, and Wilcoxon signed-rank and Kruskal–Wallis for within- and between-group differences, respectively, were used for data analyses. An average 10% (~10 kg) reduction in baseline-weight along with lower total-, android-, gynoid-, and android:gynoid-fat were observed at Week 12 (all, p < 0.05). Fifty percent of participants experienced a higher response, losing an average of 14.5 kg compared to 5.9 kg in the remaining low-response group (p < 0.0001). Hemoglobin-A1C (p = 0.005) and heart rate (p = 0.079) reduced in the high-response group only. Fat mass and A1C correlated when individuals had high android:gynoid fat (r = 0.55, p = 0.008). Gut-microbial β-diversity was associated with BMI, body fat%, and android-fat (all, p < 0.05). Microbiota of the high-response group had a higher baseline OTU-richness (p = 0.02) as well as differential abundance and/or associations with B. eggerthi, A. muciniphila, Turicibacter, Prevotella, and Christensenella (all, p/padj < 0.005). These results show that intestinal microbiota as well as sex and body composition differences may contribute to variable weight-loss response. This highlights the importance of various client features in the context of real-world weight control efforts.

BackgroundResistant starch (RS) type 4 (RS4) is a type of RS, a class of non-digestible prebiotic dietary fibers with a range of demonstrated metabolic health benefits to the host. On the other hand, bile acids (BA) have recently emerged as an important class of metabolic function mediators that involve host-microbiota interactions. RS consumption alters fecal and cecal BA in humans and rodents, respectively. The effect of RS intake on circulating BA concentrations remains unexplored in humans.Methods and resultsUsing available plasma and stool samples from our previously reported double-blind, controlled, 2-arm crossover nutrition intervention trial (Clinicaltrials.gov: NCT01887964), a liquid-chromatography/mass-spectrometry-based targeted multiple reaction monitoring, and absolute quantifications, we assessed BA changes after 12 weeks of an average 12 g/day RS4-intake. Stool BA concentrations were lower post RS4 compared to the control, the two groups consuming similar macronutrients (n = 14/group). Partial least squares-discriminant analysis revealed distinct BA signatures in stool and plasma post interventions. The increased circulating BA concentrations were further investigated using linear mixed-effect modeling that controlled for potential confounders. A higher plasma abundance of several BA species post RS4 was observed (fold increase compared to control in parenthesis): taurocholic acid (1.92), taurodeoxycholic acid (1.60), glycochenodeoxycholic acid (1.58), glycodeoxycholic acid (1.79), and deoxycholic acid (1.77) (all, p &lt; 0.05). Distinct microbiome ortholog-signatures were observed between RS4 and control groups (95% CI), derived using the Piphillin function-prediction algorithm and principal component analysis (PCA) of pre-existing 16S rRNA gene sequences. Association of Bifidobacterium adolescentis with secondary BA such as, deoxycholic acid (rho = 0.55, p = 0.05), glycodeoxycholic acid (rho = 0.65, p = 0.02), and taurodeoxycholic acid (rho = 0.56, p = 0.04) were observed in the RS4-group, but not in the control group (all, p &gt; 0.05).ConclusionOur observations indicate a previously unknown in humans- RS4-associated systemic alteration of microbiota-derived secondary BA. Follow-up investigations of BA biosynthesis in the context of RS4 may provide molecular targets to understand and manipulate microbiome-host interactions.

Scope Trimethylamine‐N‐oxide (TMAO) is a microbiota‐dependent and primarily animal‐protein‐derived proatherogenic metabolite. The ecological impact of pork—the most popular animal protein worldwide—on the human microbiome, and in the physiological context of TMAO and other biogenic amines, remains unknown. Poultry being the recommended heart‐healthier animal protein, we investigated—if pork intake results in inferior‐to‐chicken TMAO‐response while consuming a diet based on the Dietary Guidelines for Americans (DGA). Methods and Results In a randomized, controlled, all‐food‐provided, crossover, feeding trial, healthy adults consumed 156 g day−1 of lean‐pork or chicken (active‐control) as primary proteins. Mixed‐effect modeling shows pork as noninferior to chicken for circulating TMAO response and microbiota‐generated essential TMAO‐precursor—trimethylamine (97.5% CI, n = 36/protein). Markers of lipid metabolism, inflammation and oxidative stress, serum levels of betaine, choline, L‐carnitine, composition and functional‐capability of the microbiota, and association of baseline TMAO‐levels with TMAO‐response (both, r > 0.6, p = 0.0001) are nondistinguishable between the protein groups. TMAO reduction and similar shifts in microbiota and biogenic‐amine signatures postdiet in both groups indicate a background DGA‐effect. Conclusion Unlike extrapolating negative results, this study presents noninferiority‐testing based evidence. Consuming pork as a predominant protein within an omnivorous DGA‐diet does not exacerbate TMAO‐response. Results highlight the importance of understanding protein‐TMAO interactions within dietary patterns.

Objectives Recent studies have shown potential mechanisms underlying the role of bile acid (BA)-gut microbiota axis in human health and diseases. We and others have shown that resistant starch type 4 (RS4) intake modulates gut microbiota and a range of immunometabolic outcomes in humans and mice. Using available samples (#NCT01887964), we retrospectively examined the hitherto unknown effects of RS4-intake on human plasma BA. Methods In a placebo-controlled, two-arm crossover trial, 14 adults with metabolic syndrome consumed control and RS4 supplemented (30% v/v in wheat flour) diets, each for 12 weeks separated by a 2-week washout. Stealth organoleptic properties of RS4 allowed double-blinding. Overnight-fasted samples were collected before and after each diet phase. LC/MS with isotope-labeled internal standards and 16S-rDNA sequencing were used for targeted metabolite and microbiome measurements, respectively. Univariate and multivariate data were analyzed with supervised and unsupervised machine learning algorithms in R-platform. Results Differences in food ingredients, meal preparations, macronutrients, and energy intakes were minimal among participants due to following communal kitchen and dining practices (p &gt; 0.05). Being a prebiotic fiber, RS4 increased fiber consumption by 1.5-fold (p &lt; 0.001). Taurocholic acid, glycochenodeoxycholic acid, deoxycholic acid, and glycodeoxycholic acid increased in the RS4 group by 92%, 58%, 77%, and 79% respectively (all, p &lt; 0.05) and enriched species of Bacteroides, Bifidobacteria, Roseburia, Eubacterium, Ruminococcus, and Blautia. Members of these genuses are known to have high bile salt hydrolase activity, an enzyme proposed to have a cholesterol-lowering effect. One such species, Bifidobacterium adolescentis showed RS4 specific association with deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid (all, rho &gt;0.50, p &lt; 0.05). Interestingly, the parent study reported significant cholesterol-lowering effects of RS4. Conclusions RS4-enriched diet increased fiber consumption and resulted in altered microbiota-dependent secondary BA pool size and composition. Future research may help advance the understanding of the role of prebiotic fibers in BA-microbiota interactions. Funding Sources National Institute of Food and Agriculture.

Objectives Majority of Americans practice a meat-based dietary lifestyle. We hypothesized that switching between chicken and pork meats within a nutritionally balanced diet would minimally impact gut microbiota composition, biogenic amine levels, and cardiometabolic health markers in healthy, non-diabetic adults. Methods 36 eligible men and women 50 years or older were randomized into chicken and pork meat groups consuming an isocaloric (1920 kcal/day) diet. The 10 day diet arms were separated by minimum of two weeks washout period. Following the current dietary guidelines for Americans, daily meals consisting of 156 g minimally-processed meat were provided to participants. Stool, urine and blood samples were collected before and after each diet phase followed by 16S targeted metagenomics and hydrophilic interaction chromatography analyses of metabolites. Proposed outcome measures were selected based on their ability to quickly respond to dietary changes and were assessed after overnight fasting. Linear mixed effect and regression models as well as other relevant approach were applied in R studio for data analyses. Results No differential outcome was observed between the chicken and pork diet groups for body weight and body composition features, lipid panel markers, blood pressures, inflammatory and oxidative stress markers, and kidney function measures (all, P &gt; 0.05). Alpha diversity of the gut microbiome was not differential. A small number of OTU level differences in beta diversity measures were present (padj &lt; 0.05). Plasma trimethyl amine-N-oxide, trimethylamine, carnitine, and choline levels were similar between the groups. Ongoing side-by-side examination of the impact of the two meats on an extended array of over hundred biogenic amine species may reveal novel changes. Several within group effects of the intervention were observed that were non-differential between the groups. Conclusions White meat is generally perceived as healthier than red meat. Our comprehensive data suggest minimal differential metabolic impact on the host and the gut microbiota when switched between chicken (white meat) and pork (red meat). Additional assessments are needed to reflect on the long-term metabolic outcome of routine red meat intake in healthy non-vegetarian individuals. Funding Sources National Pork Board and National Institute of Food and Agriculture.