Advancing human gut microbiota research by considering gut transit time.

Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet-microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.

Diets, nutrients, genes and the microbiome: recent advances in personalised nutrition.

As individuals seek increasingly individualised nutrition and lifestyle guidance, numerous apps and nutrition programmes have emerged. However, complex individual variations in dietary behaviours, genotypes, gene expression and composition of the microbiome are increasingly recognised. Advances in digital tools and artificial intelligence can help individuals more easily track nutrient intakes and identify nutritional gaps. However, the influence of these nutrients on health outcomes can vary widely among individuals depending upon life stage, genetics and microbial composition. For example, folate may elicit favourable epigenetic effects on brain development during a critical developmental time window of pregnancy. Genes affecting vitamin B12 metabolism may lead to cardiometabolic traits that play an essential role in the context of obesity. Finally, an individual's gut microbial composition can determine their response to dietary fibre interventions during weight loss. These recent advances in understanding can lead to a more complete and integrated approach to promoting optimal health through personalised nutrition, in clinical practice settings and for individuals in their daily lives. The purpose of this review is to summarise presentations made during the DSM Science and Technology Award Symposium at the 13th European Nutrition Conference, which focused on personalised nutrition and novel technologies for health in the modern world.

Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis.

BACKGROUND/OBJECTIVES: Individuals with high pre-treatment bacterial Prevotella-to-Bacteroides (P/B) ratio have been reported to lose more body weight on diets high in fiber than subjects with a low P/B ratio. Therefore, the aim of the present study was to examine potential differences in dietary weight loss responses between participants with low and high P/B. SUBJECTS/METHODS: Eighty overweight participants were randomized (52 completed) to a 500 kcal/d energy deficit diet with a macronutrient composition of 30 energy percentage (E%) fat, 52 E% carbohydrate and 18 E% protein either high (≈1500 mg calcium/day) or low ( ≤ 600 mg calcium/day) in dairy products for 24 weeks. Body weight, body fat, and dietary intake (by 7-day dietary records) were determined. Individuals were dichotomized according to their pre-treatment P/B ratio derived from 16S rRNA gene sequencing of collected fecal samples to test the potential modification of dietary effects using linear mixed models. RESULTS: Independent of the randomized diets, individuals with high P/B lost 3.8 kg (95%CI, 1.8,5.8; P < 0.001) more body weight and 3.8 kg (95% CI, 1.1, 6.5; P = 0.005) more body fat compared to individuals with low P/B. After adjustment for multiple covariates, individuals with high P/B ratio lost 8.3 kg (95% CI, 5.8;10.9, P < 0.001) more body weight when consuming above compared to below 30 g fiber/10MJ whereas this weight loss was 3.2 kg (95% CI, 0.8;5.5, P = 0.008) among individuals with low P/B ratio [Mean difference: 5.1 kg (95% CI, 1.7;8.6, P = 0.003)]. Partial correlation coefficients between fiber intake and weight change was 0.90 (P < 0.001) among individuals with high P/B ratio and 0.25 (P = 0.29) among individuals with low P/B ratio. CONCLUSIONS: Individuals with high P/B lost more body weight and body fat compared to individuals with low P/B, confirming that individuals with a high P/B are more susceptible to weight loss on a diet rich in fiber.

Prevotella Abundance Predicts Weight Loss Success in Healthy, Overweight Adults Consuming a Whole-Grain Diet Ad Libitum: A Post Hoc Analysis of a 6-Wk Randomized Controlled Trial.

BACKGROUND: The key to effective weight loss may be to match diet and gut microbes, since recent studies have found that subjects with high Prevotella abundances in their gut microbiota lose more weight on diets rich in fiber than subjects with low Prevotella abundances. OBJECTIVES: We reanalyzed a 6-wk, parallel, randomized trial to investigate difference in body weight changes when participants, stratified by fecal microbiota composition, consumed ad libitum a whole-grain (WG) or a refined-wheat (RW) diet. METHODS: We stratified 46 (19 men, 27 women; ages 30-65 y) healthy, overweight adults by baseline Prevotella-to-Bacteroides ratios and Prevotella abundances. Subjects with no Prevotella were analyzed separately (n = 24). Compared with the RW diet (mean = 221 g/d), the WG diet (mean = 228 g/d) had a higher fiber content (33 g/d compared with 23 g/d). Linear mixed models and correlations were applied to link 6-wk changes in body weights and metabolic and microbiota markers, according to Prevotella groups and diets. RESULTS: The Prevotella abundances correlated inversely with weight changes (r = -0.34; P = 0.043). Consequently, subjects with high Prevotella abundances (n = 15) spontaneously lost 1.80 kg (95% CI: -3.23, -0.37 kg; P = 0.013) more on the WG diet than on the RW diet, whereas those with low Prevotella abundances (n = 31) were weight stable (-0.22 kg; 95% CI: -1.40, 0.96 kg; P = 0.72). Thus, the mean difference between the Prevotella groups was 2.02 kg (95% CI: -3.87, -0.17 kg; P = 0.032). Subjects with no Prevotella lost 1.59 kg (95% CI: -2.65, -0.52 kg; P = 0.004) more on the WG diet than on the RW diet. No 6-wk changes in appetite sensations, glucose metabolisms, or fecal SCFAs were associated with the Prevotella groups. CONCLUSIONS: Healthy, overweight adults with high Prevotella abundances lost more weight than subjects with low Prevotella abundances when consuming a diet rich in WG and fiber ad libitum for 6 wk. This further supports enterotypes as a potential biomarker in personalized nutrition for obesity management. This t rial was registered at clinicaltrials.gov as NCT02358122.

Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new nordic diet.

It has been suggested that the human gut microbiota can be divided into enterotypes based on the abundance of specific bacterial groups; however, the biological significance and stability of these enterotypes remain unresolved. Here, we demonstrated that subjects (n = 62) 18 to 65 years old with central obesity and components of metabolic syndrome could be grouped into two discrete groups simply by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Furthermore, we showed that these groups remained stable during a 6-month, controlled dietary intervention, where the effect of consuming a diet in accord with the new Nordic diet (NND) recommendations as opposed to consuming the average Danish diet (ADD) on the gut microbiota was investigated. In this study, subjects (with and without stratification according to P/B ratio) did not reveal significant changes in 35 selected bacterial taxa quantified by quantitative PCR (ADD compared to NND) resulting from the dietary interventions. However, we found higher total plasma cholesterol within the high-P/B group than in the low-P/B group after the intervention. We propose that stratification of humans based simply on their P/B ratio could allow better assessment of possible effects of interventions on the gut microbiota and physiological biomarkers.

Towards nutrition with precision: unlocking biomarkers as dietary assessment tools.

Precision nutrition requires precise tools to monitor dietary habits. Yet current dietary assessment instruments are subjective, limiting our understanding of the causal relationships between diet and health. Biomarkers of food intake (BFIs) hold promise to increase the objectivity and accuracy of dietary assessment, enabling adjustment for compliance and misreporting. Here, we update current concepts and provide a comprehensive overview of BFIs measured in urine and blood. We rank BFIs based on a four-level utility scale to guide selection and identify combinations of BFIs that specifically reflect complex food intakes, making them applicable as dietary instruments. We discuss the main challenges in biomarker development and illustrate key solutions for the application of BFIs in human studies, highlighting different strategies for selecting and combining BFIs to support specific study designs. Finally, we present a roadmap for BFI development and implementation to leverage current knowledge and enable precision in nutrition research.

Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota.

Tryptophan is catabolized by gut microorganisms resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. How gut microbial tryptophan metabolism is directed towards indole, associated with chronic kidney disease, or towards protective indolelactic acid (ILA) and indolepropionic acid (IPA) is unclear. Here we used in vitro culturing and animal experiments to assess gut microbial competition for tryptophan and the resulting metabolites in a controlled three-species defined community and in complex undefined human faecal communities. The generation of specific tryptophan-derived metabolites was not predominantly determined by the abundance of tryptophan-metabolizing bacteria, but rather by substrate-dependent regulation of specific metabolic pathways. Indole-producing Escherichia coli and ILA- and IPA-producing Clostridium sporogenes competed for tryptophan within the three-species community in vitro and in vivo. Importantly, fibre-degrading Bacteroides thetaiotaomicron affected this competition by cross-feeding monosaccharides to E. coli. This inhibited indole production through catabolite repression, thus making more tryptophan available to C. sporogenes, resulting in increased ILA and IPA production. The fibre-dependent reduction in indole was confirmed using human faecal cultures and faecal-microbiota-transplanted gnotobiotic mice. Our findings explain why consumption of fermentable fibres suppresses indole production but promotes the generation of other tryptophan metabolites associated with health benefits.

Human milk oligosaccharides modify the strength of priority effects in the Bifidobacterium community assembly during infancy.

Despite the significant role of the gut microbiota in infant health and development, little is known about the ecological processes determining gut microbial community assembly. According to ecology theory, the timing and order of arrival of microbial species into an ecosystem affect microbial community assembly, a phenomenon termed priority effects. Bifidobacterium species are recognized as highly abundant early colonizers of the infant's gut, partly due to their ability to selectively utilize human milk oligosaccharides (HMOs) from breast milk. However, the role of priority effects in Bifidobacterium community assembly remains unclear. Here, we investigated the Bifidobacterium community assembly in the gut of 25 breastfed Danish infants longitudinally sampled throughout the first 6 months of life. Our results showed that the breastfed infants were often initially, but temporarily, dominated by suboptimal HMO-utilizing Bifidobacterium taxa, such as B. longum subsp. longum, before more efficient HMO-utilizers such as B. longum subsp. infantis, replaced the first colonizer as the dominant Bifidobacterium taxon. Subsequently, we validated this observation using gnotobiotic mice sequentially colonized with B. longum subsp. longum and B. longum subsp. infantis or vice versa, with or without supplementation of HMOs in the drinking water. The results showed that in the absence of HMOs, order of arrival determined dominance. Yet, when mice were supplemented with HMOs the strength of priority effects diminished, and B. longum subsp. infantis dominated regardless of colonization order. Our data demonstrate that the arrival order of Bifidobacterium taxa and the deterministic force of breast milk-derived HMOs, dictate Bifidobacterium community assembly in the infant's gut.

Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life.

The development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been of interest for decades, the focus on gut microbial metabolism and the resulting small molecules (metabolites) has been rather limited. However, technological and computational advances are now enabling researchers to profile the plethora of metabolites in the infant gut, allowing for improved understanding of how gut microbial-derived metabolites drive microbiome community structuring and host-microbial interactions. Here, we review the current knowledge on development of the infant gut microbiota and metabolism within the first year of life, and discuss how these microbial metabolites are key for enhancing our basic understanding of interactions during the early life developmental window.

Key bacterial taxa determine longitudinal dynamics of aromatic amino acid catabolism in infants' gut.

The development of the gut microbiota in early life is linked to metabolic, neuronal, and immunological development. Recent studies have shown that bacterial production of short-chain fatty acids (SCFAs) and aromatic amino acid (AAA) catabolites in the gut can mediate host-microbe interactions. However, the dynamics of these microbiota-derived metabolites and the key bacterial taxa producing AAA catabolites during infancy are largely unknown. Here, we investigated the longitudinal dynamics of the microbiota and microbiota-derived SCFAs and AAA catabolites in more than 200 fecal samples from 25 healthy breast- or mixed-fed Danish infants during the first 6 months of life. We found that the gut microbiota composition and metabolism were highly individual but showed significant development over time. SCFAs and specific groups of AAA catabolites showed distinct temporal abundance patterns. Furthermore, we identified bacterial taxa responsible for the generation of AAA catabolites by associating the dynamics of gut microbial taxa and AAA catabolites and subsequently validating these associations in vitro by cultivation of strains representing the associated taxa. In addition to specific Bifidobacterium species being the main producers of aromatic lactic acids, we identified Peptostreptococcus anaerobius as the main producer of aromatic propionic acids, Ruminococcus gnavus as a main producer of tryptamine, and Enterococcus species as main tyramine producers in infants' gut. Thus, our results showcase the temporal dynamics of key gut microbial metabolites in early life and demonstrate that the appearance and abundance of specific AAA catabolites result from the appearance and abundance of specific key bacterial taxa in infants' gut.

Supplementation with inulin-type fructans affects gut microbiota and attenuates some of the cardiometabolic benefits of a plant-based diet in individuals with overweight or obesity.

Background: The gut microbiota has emerged as a potential therapeutic target to improve the management of obesity and its comorbidities. Objective: We investigated the impact of a high fiber (∼38 g/d) plant-based diet, consumed ad libitum, with or without added inulin-type fructans (ITF), on the gut microbiota composition and cardiometabolic outcomes in subjects with obesity. We also tested if baseline Prevotella/Bacteroides (P/B) ratio predicts weight loss outcomes. Methods: This is a secondary exploratory analysis from the PREVENTOMICS study, in which 100 subjects (82 completers) aged 18-65 years with body mass index 27-40 kg/m2 were randomized to 10 weeks of double-blinded treatment with a personalized or a generic plant-based diet. Changes from baseline to end-of-trial in gut microbiota composition (16S rRNA gene amplicon sequencing), body composition, cardiometabolic health and inflammatory markers were evaluated in the whole cohort (n = 82), and also compared in the subgroup of subjects who were supplemented with an additional 20 g/d ITF-prebiotics (n = 21) or their controls (n = 22). Results: In response to the plant-based diet, all subjects lost weight (-3.2 [95% CI -3.9, -2.5] kg) and experienced significant improvements in body composition and cardiometabolic health indices. Addition of ITF to the plant-based diet reduced microbial diversity (Shannon index) and selectively increased Bifidobacterium and Faecalibacterium (q < 0.05). The change in the latter was significantly associated with higher values of insulin and HOMA-IR and lower HDL cholesterol. In addition, the LDL:HDL ratio and the concentrations of IL-10, MCP-1 and TNFα were significantly elevated in the ITF-subgroup. There was no relationship between baseline P/B ratio and changes in body weight (r = -0.07, p = 0.53). Conclusion: A plant-based diet consumed ad libitum modestly decreases body weight and has multiple health benefits in individuals with obesity. Addition of ITF-prebiotics on top this naturally fiber-rich background selectively changes gut microbiota composition and attenuates some of the realized cardiometabolic benefits. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04590989], identifier [NCT04590989].

Effects of a wholegrain-rich diet on markers of colonic fermentation and bowel function and their associations with the gut microbiome: a randomised controlled cross-over trial.

Background: Diets rich in whole grains are associated with health benefits. Yet, it remains unclear whether the benefits are mediated by changes in gut function and fermentation. Objective: We explored the effects of whole-grain vs. refined-grain diets on markers of colonic fermentation and bowel function, as well as their associations with the gut microbiome. Methods: Fifty overweight individuals with increased metabolic risk and a high habitual intake of whole grains (~69 g/day) completed a randomised cross-over trial with two 8-week dietary intervention periods comprising a whole-grain diet (≥75 g/day) and a refined-grain diet (<10 g/day), separated by a washout period of ≥6 weeks. A range of markers of colonic fermentation and bowel function were assessed before and after each intervention. Results: The whole-grain diet increased the levels of faecal butyrate (p = 0.015) and caproate (p = 0.013) compared to the refined-grain diet. No changes in other faecal SCFA, BCFA or urinary levels of microbial-derived proteolytic markers between the two interventions were observed. Similarly, faecal pH remained unchanged. Faecal pH did however increase (p = 0.030) after the refined-grain diet compared to the baseline. Stool frequency was lower at the end of the refined-grain period compared to the end of the whole-grain diet (p = 0.001). No difference in faecal water content was observed between the intervention periods, however, faecal water content increased following the whole-grain period compared to the baseline (p = 0.007). Dry stool energy density was unaffected by the dietary interventions. Nevertheless, it explained 4.7% of the gut microbiome variation at the end of the refined-grain diet, while faecal pH and colonic transit time explained 4.3 and 5%, respectively. Several butyrate-producers (e.g., Faecalibacterium, Roseburia, Butyriciococcus) were inversely associated with colonic transit time and/or faecal pH, while the mucin-degraders Akkermansia and Ruminococcaceae showed the opposite association. Conclusion: Compared with the refined-grain diet, the whole-grain diet increased faecal butyrate and caproate concentrations as well as stool frequency, emphasising that differences between whole and refined grains affect both colonic fermentation and bowel habits.

Personal diet-microbiota interactions and weight loss.

The aim of this review is to provide an overview of how person-specific interactions between diet and the gut microbiota could play a role in affecting diet-induced weight loss responses. The highly person-specific gut microbiota, which is shaped by our diet, secretes digestive enzymes and molecules that affect digestion in the colon. Therefore, weight loss responses could in part depend on personal colonic fermentation responses, which affect energy extraction of food and production of microbial metabolites, such as short-chain fatty acids (SCFAs), which exert various effects on host metabolism. Colonic fermentation is the net result of the complex interplay between availability of dietary substrates, the functional capacity of the gut microbiome and environmental (abiotic) factors in the gut such as pH and transit time. While animal studies have demonstrated that the gut microbiota can causally affect obesity, causal and mechanistic evidence from human studies is still largely lacking. However, recent human studies have proposed that the baseline gut microbiota composition may predict diet-induced weight loss-responses. In particular, individuals characterised by high relative abundance of Prevotella have been found to lose more weight on diets rich in dietary fibre compared to individuals with low Prevotella abundance. Although harnessing of personal diet-microbiota interactions holds promise for more personalised nutrition and obesity management strategies to improve human health, there is currently insufficient evidence to unequivocally link the gut microbiota and weight loss in human subjects. To move the field forward, a greater understanding of the mechanistic underpinnings of personal diet-microbiota interactions is needed.

Prevotella abundance and salivary amylase gene copy number predict fat loss in response to wholegrain diets.

Background: Salivary amylase (AMY1) gene copy number (CN) and Prevotella abundance in the gut are involved in carbohydrate digestion in the upper and lower gastrointestinal tract, respectively; and have been suggested as prognostic biomarkers for weight loss among overweight individuals consuming diets rich in fiber and wholegrains. Objective: We hypothesized that Prevotella abundance would be linked to greater loss of body fat after wholegrain consumption among individuals with low AMY1 CN, but not in those with high AMY1 CN. Methods: We reanalyzed data from two independent randomized ad libitum wholegrain interventions (fiber intake ∼33 g/d for 6-8 weeks), to investigate the relationship between baseline Prevotella abundance and body fat loss among healthy, overweight participants stratified into two groups by median AMY1 CN. Individuals with no detected Prevotella spp. were excluded from the main analysis. Results: In both studies, individuals with low AMY1 CN exhibited a positive correlation between baseline Prevotella abundance and fat loss after consuming the wholegrain diet (r > 0.5, P < 0.05), but no correlation among participants with high AMY1 CN (P ≥ 0.6). Following consumption of the refined wheat control diets, there were no associations between baseline Prevotella abundance and changes in body fat in any of the AMY1 groups. Conclusion: These results suggest that Prevotella abundance together with AMY1 CN can help predict fat loss in response to ad libitum wholegrain diets, highlighting the potential of these biomarkers in personalized obesity management.

Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes.

BACKGROUND: It has been hypothesised that the gut microbiota causally affects obesity via its capacity to extract energy from the diet. Yet, evidence elucidating the role of particular human microbial community structures and determinants of microbiota-dependent energy harvest is lacking. RESULTS: Here, we investigated whether energy extraction from the diet in 85 overweight adults, estimated by dry stool energy density, was associated with intestinal transit time and variations in microbial community diversity and overall structure stratified as enterotypes. We hypothesised that a slower intestinal transit would allow for more energy extraction. However, opposite of what we expected, the stool energy density was positively associated with intestinal transit time. Stratifications into enterotypes showed that individuals with a Bacteroides enterotype (B-type) had significantly lower stool energy density, shorter intestinal transit times, and lower alpha-diversity compared to individuals with a Ruminococcaceae enterotype (R-type). The Prevotella (P-type) individuals appeared in between the B- and R-type. The differences in stool energy density between enterotypes were not explained by differences in habitual diet, intake of dietary fibre or faecal bacterial cell counts. However, the R-type individuals showed higher urinary and faecal levels of microbial-derived proteolytic metabolites compared to the B-type, suggesting increased colonic proteolysis in the R-type individuals. This could imply a less effective colonic energy extraction in the R-type individuals compared to the B-type individuals. Notably, the R-type had significantly lower body weight compared to the B-type. CONCLUSIONS: Our findings suggest that gut microbial energy harvest is diversified among individuals by intestinal transit time and associated gut microbiome ecosystem variations. A better understanding of these associations could support the development of personalised nutrition and improved weight-loss strategies. Video Abstract.

A synthetic consortium of 100 gut commensals modulates the composition and function in a colon model of the microbiome of elderly subjects.

Administration of cultured gut isolates holds promise for modulating the altered composition and function of the microbiota in older subjects, and for promoting their health. From among 692 initial isolates, we selected 100 gut commensal strains (MCC100) based on emulating the gut microbiota of healthy subjects, and retaining strain diversity within selected species. MCC100 susceptibility to seven antibiotics was determined, and their genomes were screened for virulence factor, antimicrobial resistance and bacteriocin genes. Supplementation of healthy and frail elderly microbiota types with the MCC100 in an in vitro colon model increased alpha-diversity, raised relative abundance of taxa including Blautia luti, Bacteroides fragilis, and Sutterella wadsworthensis; and introduced taxa such as Bifidobacterium spp. Microbiota changes correlated with higher levels of branched chain amino acids, which are health-associated in elderly. The study establishes that the MCC100 consortium can modulate older subjects' microbiota composition and associated metabolome in vitro, paving the way for pre-clinical and human trials.

Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut.

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+ T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.

Pretreatment Prevotella-to-Bacteroides ratio and markers of glucose metabolism as prognostic markers for dietary weight loss maintenance.

BACKGROUND/OBJECTIVES: Pre-treatment gut microbial Prevotella-to-Bacteroides (P/B) ratio and markers of glucose metabolism (i.e., fasting glucose and insulin) have been suggested as biomarkers for optimal weight management. However, both biomarkers need further validation, and the interactions between them for optimal weight management are largely unknown. To investigate differences in weight loss maintenance between subjects with low and high P/B ratio and the potential interactions with markers of glucose metabolism and dietary fiber intake. SUBJECTS/METHODS: Following an 8-week weight loss period using meal replacement products, subjects losing ≥ 8% of their initial body weight were randomized to one of three protein supplements or maltodextrin for a 24-week weight maintenance period. Habitual diet was consumed along with the supplements expected to constitute 10-15% of total energy. For this analysis we stratified the participants into low and high strata based on median values of pre-intervention P/B ratio, pre-weight loss Homeostatic model assessment of insulin resistance (HOMA-IR) (<2.33 or > 2.33), and dietary fiber intake during the intervention (< 28.5 or > 28.5 g/10 MJ). RESULTS: Regardless of weight maintenance regimen, subjects with high P/B ratio (n = 63) regained 1.5 (95% CI 0.4, 2.7) kg body weight (P = 0.007) more than subjects with low P/B ratio (n = 63). The regain among subjects with high P/B ratio was particular evident if HOMA-IR was high and dietary fiber intake was low. Consequently, in the high P/B strata, subjects with high HOMA-IR and low fiber intake (n = 17) regained 5.3 (95% CI 3.3, 7.3) kg (P < 0.001) more body weight compared with participants with low HOMA-IR and high fiber intake (n = 16). CONCLUSIONS: Subjects with high P/B ratio were more susceptible to regain body weight compared with subjects with low P/B ratio, especially when dietary fiber intake was low and glucose metabolism was impaired. These observations underline that both the P/B ratio and markers of glucose metabolism should be considered as important biomarkers within personalized nutrition for optimal weight management.

The Gut Microbiome and Abiotic Factors as Potential Determinants of Postprandial Glucose Responses: A Single-Arm Meal Study.

The gut microbiome has combined with other person-specific information, such as blood parameters, dietary habits, anthropometrics, and physical activity been found to predict personalized postprandial glucose responses (PPGRs) to various foods. Yet, the contributions of specific microbiome taxa, measures of fermentation, and abiotic factors in the colon to glycemic control remain elusive. We tested whether PPGRs 60 min after a standardized breakfast was associated with gut microbial α-diversity (primary outcome) and explored whether postprandial responses of glucose and insulin were associated with specific microbiome taxa, colonic fermentation as reflected by fecal short-chain fatty acids (SCFAs), and breath hydrogen and methane exhalation, as well as abiotic factors including fecal pH, fecal water content, fecal energy density, intestinal transit time (ITT), and stool consistency. A single-arm meal trial was conducted. A total of 31 healthy (24 female and seven male) subjects consumed a standardized evening meal and a subsequent standardized breakfast (1,499 kJ) where blood was collected for analysis of postprandial glucose and insulin responses. PPGRs to the same breakfast varied across the healthy subjects. The largest inter-individual variability in PPGRs was observed 60 min after the meal but was not associated with gut microbial α-diversity. In addition, no significant associations were observed between postprandial responses and specific taxa of the gut microbiome, measures of colonic fermentation, ITT, or other abiotic factors. However, fasting glucose concentrations were negatively associated with ITT, and fasting insulin was positively associated with fasting breath hydrogen. In conclusion, the gut microbiome, measures of colonic fermentation, and abiotic factors were not shown to be significantly associated with variability in postprandial responses, suggesting that contributions of the gut microbiome, colonic fermentation, and abiotic factors to PPGRs may be subtle in healthy adults.

Pretreatment Prevotella-to-Bacteroides ratio and salivary amylase gene copy number as prognostic markers for dietary weight loss.

BACKGROUND: The inconsistent link observed between salivary amylase gene copy number (AMY1 CN) and weight management is likely modified by diet and microbiome. OBJECTIVE: Based on analysis of a previously published study, we investigated the hypothesis that interaction between diet, Prevotella-to-Bacteriodes ratio (P/B ratio), and AMY1 CN influence weight change. METHODS: Sixty-two people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber, whole grain, intrinsic sugars, and starch or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Before subjects were randomly assigned to receive the NND or ADD diet, blood and fecal samples were collected, from which AMY1 CN and P/B ratio, respectively, were determined. Body weight change was described by using linear mixed models, including biomarker [log10(P/B ratio) and/or AMY1 CN] diet-group interactions. RESULTS: Baseline means ± SDs of log10(P/B ratio) and AMY1 CN were -2.1 ± 1.8 and 6.6 ± 2.4, respectively. Baseline P/B ratio predicted a 0.99-kg/unit (95% CI: 0.40, 1.57; n = 54; P < 0.001) higher weight loss for those subjects on the NND compared with those on the ADD diet, whereas AMY1 CN was not found to predict weight loss differences between the NND and ADD groups [0.05 kg/CN (95% CI: -0.40, 0.51; n = 54; P = 0.83)]. However, among subjects with low AMY1 CN (<6.5 copies), baseline P/B ratio predicted a 2.12-kg/unit (95% CI: 1.37, 2.88; n = 30; P < 0.001) higher weight loss for the NND group than the ADD group. No such differences in weight loss were found among subjects in both groups with high AMY1 CN [-0.17 kg/unit (95% CI: -1.01, 0.66; n = 24; P = 0.68)]. CONCLUSIONS: The combined use of low AMY1 CN and pretreatment P/B ratio for weight loss prediction led to highly individualized weight loss results with the introduction of more fiber, whole grain, intrinsic sugars, and starch in the diet. These preliminary observations suggest that more undigested starch reaches the colon in individuals with low AMY1 CN, and that the fate of this starch depends on the gut microbiota composition. This trial was registered at clinicaltrials.gov as NCT01195610.