Complex carbohydrate utilization by gut bacteria modulates host food preference.

The gut microbiota interacts directly with dietary nutrients and has the ability to modify host feeding behavior, but the underlying mechanisms remain poorly understood. Select gut bacteria digest complex carbohydrates that are non-digestible by the host and liberate metabolites that serve as additional energy sources and pleiotropic signaling molecules. Here we use a gnotobiotic mouse model to examine how differential fructose polysaccharide metabolism by commensal gut bacteria influences host preference for diets containing these carbohydrates. Bacteroides thetaiotaomicron and Bacteroides ovatus selectively ferment fructans with different glycosidic linkages: B. thetaiotaomicron ferments levan with ß2-6 linkages, whereas B. ovatus ferments inulin with ß2-1 linkages. Since inulin and levan are both fructose polymers, inulin and levan diet have similar perceptual salience to mice. We find that mice colonized with B. thetaiotaomicron prefer the non-fermentable inulin diet, while mice colonized with B. ovatus prefer the non-fermentable levan diet. Knockout of bacterial fructan utilization genes abrogates this preference, whereas swapping the fermentation ability of B. thetaiotaomicron to inulin confers host preference for the levan diet. Bacterial fructan fermentation and host behavioral preference for the non-fermentable fructan are associated with increased neuronal activation in the arcuate nucleus of the hypothalamus, a key brain region for appetite regulation. These results reveal that selective nutrient metabolism by gut bacteria contributes to host associative learning of dietary preference, and further informs fundamental understanding of the biological determinants of food choice.

Metal-Organic Frameworks for Phthalate Capture.

Indoor air contamination by phthalate ester (PAE) derivatives has become a significant concern since traces of PAEs can cause endocrine disruption, among other health issues. PAE abatement from the environment is thus mandatory to further ensure a good quality of indoor air. Herein, we explored the physisorption-based capture of volatile PAEs by metal-organic frameworks (MOFs). A high-throughput computational screening approach was first applied on databases compiling more than 20,000 MOF structures in order to identify the best MOFs for adsorbing traces of dimethyl phthalate (DMP), considered as a representative molecule of the family of PAE contaminants. Among the 20 top candidates, MOF-74(Ni), which combines substantial DMP uptake at the 10 ppm concentration level (∼0.20 g g-1) with high adsorption enthalpy at infinite dilution (-ΔHads(DMP),0 = 109.9 kJ mol-1), was revealed as an excellent porous material to capture airborne DMP. This prediction was validated by further experiments: gravimetric sorption isotherms were carried out on MOF-74(Ni), replacing DMP by dimethyl maleate (DMM), a molecule with a higher vapor pressure and indeed easier to manipulate compared to DMP while mimicking the adsorption behavior of DMP by MOFs, as evidenced by Monte Carlo calculations. Notably, saturation of DMM by MOF-74(Ni) (∼0.35 g g-1 at 343 K) occurs at very low equivalent concentration of the sorbate, i.e., 15 ppm, while half of the DMM molecules remain trapped in the MOF pores, even by heating the system up to 473 K under vacuum. This computational-experimental study reveals for the first time the potential of MOFs for the capture of phthalate ester contaminants as vapors of key importance to address indoor air quality issues.

Bifidobacterium infantis utilizes N-acetylglucosamine-containing human milk oligosaccharides as a nitrogen source.

Bifidobacterium longum subsp. infantis (B. infantis) utilizes oligosaccharides secreted in human milk as a carbohydrate source. These human milk oligosaccharides (HMOs) integrate the nitrogenous residue N-acetylglucosamine (NAG), although HMO nitrogen utilization has not been described to date. Herein, we characterize the B. infantis nitrogen utilization phenotype on two NAG-containing HMO species, LNT and LNnT. This was characterized through in vitro growth kinetics, incorporation of isotopically labeled NAG nitrogen into the proteome, as well as modulation of intracellular 2-oxoglutarate levels while utilizing HMO nitrogen. Further support is provided by comparative transcriptomics and proteomics that identified global regulatory networks deployed during HMO nitrogen utilization. The aggregate data demonstrate that B. infantis strains utilize HMO nitrogen with the potential to significantly impact fundamental and clinical studies, as well as enable applications.

Bifidobacterium longum subsp. infantis utilizes human milk urea to recycle nitrogen within the infant gut microbiome.

Human milk guides the structure and function of microbial commensal communities that colonize the nursing infant gut. Indigestible molecules dissolved in human milk establish a microbiome often dominated by bifidobacteria capable of utilizing these substrates. Interestingly, urea accounts for ~15% of total human milk nitrogen, representing a potential reservoir for microbiota that may be salvaged for critical metabolic operations during lactation and neonatal development. Accordingly, B. infantis strains are competent for urea nitrogen utilization, constituting a previously hypothetical phenotype in commensal bacteria hosted by humans. Urease gene expression, downstream nitrogen metabolic pathways, and enzymatic activity are induced during urea utilization to yield elevated ammonia concentrations. Moreover, biosynthetic networks relevant to infant nutrition and development are transcriptionally responsive to urea utilization including branched chain and other essential amino acids. Importantly, isotopically labeled urea nitrogen is broadly distributed throughout the expressed B. infantis proteome. This incisively demonstrates that the previously inaccessible urea nitrogen is incorporated into microbial products available for infant host utilization. In aggregate, B. infantis possesses the requisite phenotypic foundation to participate in human milk urea nitrogen recycling within its infant host and thus may be a key contributor to nitrogen homeostasis early in life.

Interactions between the gut microbiome and ketogenic diet in refractory epilepsy.

Epilepsy is one of the most common neurological diseases globally, afflicting approximately 50 million people worldwide. While many antiepileptic drugs exist, an estimated one-third of individuals do not respond to available medications. The high fat, low carbohydrate ketogenic diet (KD) has been used to treat refractory epilepsy in cases when existing antiepileptic drugs fail. However, there are many variations of the KD, each of which varies greatly in its efficacy and side effects. Increasing evidence suggests that interactions between the KD and gut microbiome may modulate the effects of the diet on host physiology. Herein, we review existing evidence of microbiome differences in epileptic individuals compared to healthy controls. We highlight in particular both clinical and animal studies revealing effects of the KD on the composition and function of the microbiome, as well as proof-of-concept animal studies that implicate the microbiome in the antiseizure effects of the KD. We further synthesize findings suggesting that variations in clinical KD formulations may differentially influence host physiology and discuss the gut microbial interactions with specific dietary factors that may play a role. Overall, understanding interactions between the gut microbiota and specific nutritional components of clinical KDs could reveal foundational mechanisms that underlie the effectiveness, variability, and side effects of different KDs, with the potential to lead to precision nutritional and microbiome-based approaches to treat refractory epilepsy.

Airborne Toluene Detection Using Metal-Organic Frameworks.

The pollution of indoor air is a major worldwide concern in our modern society for people's comfort, health, and safety. In particular, toluene, present in many substances including paints, thinners, candles, leathers, cosmetics, inks, and glues, affects the human health even at very low concentrations throughout its action on the central nervous system. Its prevalence in many workplace environments can fluctuate considerably, which led to firm regulation with exposure limits varying between 50 and 400 ppm depending on exposure time. This therefore requires the development of technologies for an accurate detection of this contaminant. Metal-organic frameworks have been proposed as promising candidates to detect and monitor a series of molecules at even extremely low concentrations owing to the high tunability of their functionality. Herein, a high-throughput Monte Carlo screening approach was devised to identify the best MOFs from the computation-ready, experimental (CoRE) metal-organic framework (MOF) density-derived electrostatic and chemical (DDEC) database for the selective capture of toluene from air at room temperature, with the consideration of a ternary mixture composed of extremely low-level concentration of toluene (10 ppm) in oxygen and nitrogen to mimic the composition of air. An aluminum MOF, DUT-4, with channel-like micropores was identified as an excellent candidate for the selective adsorption of toluene from air with a predicted adsorption uptake of 0.5 g/g at 10 ppm concentration and room temperature. The toluene adsorption behavior of DUT-4 at low equivalent concentrations, alongside its sensing performance, was further experimentally investigated by its incorporation in a quartz crystal microbalance sensor, confirming the promises of DUT-4. Decisively, the resulting high sensitivity and fast kinetics of our developed sensor highlight the applicability of this hand-in-hand computational-experimental methodology to porous material screening for sensing applications.

MIL-101(Cr) MOF as an Effective Siloxane Sensor.

Volatile methylsiloxanes (VMSs) are common silicone degradation byproducts that cause serious concern for the contamination of sensitive electronics and optics, among others. With the goal of fast, online detection of VMS, we herein highlight the mesoporous MIL-101(Cr) MOF as a promising mass sensing layer for integration with a quartz crystal microbalance (QCM), using an in-house modified gravimetric adsorption system capable of achieving extremely low concentrations of siloxane D4 (down to 0.04 ppm), targeting applications for monitoring in indoor spaces and spacecraft. Our developed MIL-101(Cr)@QCM sensor achieves near-perfect reversibility with no hysteresis alongside excellent repeatability over cycling and fast response/recovery times under 1 min. We attribute this capability to optimum host/guest interactions as uncovered through molecular simulations.

Are changes in the gut microbiome a contributor or consequence of autism-why not both?

Alterations in the gut microbiome have been associated with autism spectrum disorder (ASD), but whether they are a cause, effect, or confounder remains unclear. In a recent issue of Cell, Yap and colleagues report that ASD-associated microbiota changes are likely a consequence of low diet diversity.1.

Cranberry Proanthocyanidins and Dietary Oligosaccharides Synergistically Modulate Lactobacillus plantarum Physiology.

Plant-based foods contain bioactive compounds such as polyphenols that resist digestion and potentially benefit the host through interactions with their resident microbiota. Based on previous observations, we hypothesized that the probiotic Lactobacillus plantarum interacts with cranberry polyphenols and dietary oligosaccharides to synergistically impact its physiology. In this study, L. plantarum ATCC BAA-793 was grown on dietary oligosaccharides, including cranberry xyloglucans, fructooligosaccharides, and human milk oligosaccharides, in conjunction with proanthocyanidins (PACs) extracted from cranberries. As a result, L. plantarum exhibits a differential physiological response to cranberry PACs dependent on the carbohydrate source and polyphenol fraction introduced. Of the two PAC extracts evaluated, the PAC1 fraction contains higher concentrations of PACs and increased growth regardless of the oligosaccharide, whereas PAC2 positively modulates its growth during xyloglucan metabolism. Interestingly, fructooligosaccharides (FOS) are efficiently utilized in the presence of PAC1, as this L. plantarum strain does not utilize this substrate typically. Relative to glucose, oligosaccharide metabolism increases the ratio of secreted acetic acid to lactic acid. The PAC2 fraction differentially increases this ratio during cranberry xyloglucan fermentation compared with PAC1. The global transcriptome links the expression of putative polyphenol degradation genes and networks and metabolic phenotypes.

Determinants of Travel Participation and Experiences of Wheelchair Users Traveling to the Bodrum Region: A Qualitative Study.

Although the number of people with disabilities and types of disability increases day by day, a sufficient point has not been reached regarding accessible tourism. The participation rate of people with disabilities (PWDS) in tourism activities is low, and there is a big gap in the travel and accommodation sector in this regard. Studies of previous scholars have concluded that the accessible tourism market is a significant and profitable area, but determinants of participation to travel and process of travel, such as wheelchair user expectations, are consistently ignored by the tourism industry. The main purpose of this study is to determine the determinants of travel by examining the motivations, expectations, processes and experiences of PWDS using wheelchairs to participate in tourism. Research was performed in Turkey's Bodrum district; 25 wheelchair users were included in the study. The keywords that emerged in the theoretical framework in light of the answers given to 39 open-ended questions online were coded in the Nvivo program. The results showed that wheelchair users intended to go on vacation but were less motivated to participate due to the lack of travel conditions. Wheelchair travelers argued that a companion was required for an enjoyable holiday that could meet their needs. In addition, the results revealed that the types of wheelchairs used by disabled passengers differ. The disabled stated that the wheelchairs they use in daily life are not suitable for use on the beach, sand or water. Despite the economic, social and technological change opportunities, basic tourism service expectations of PWDS are not met. This research project is a comprehensive study that makes determinations in terms of examining the social status of disabled people in terms of social sciences, examining the place and importance of disabled tourists in the market and eliminating the deficiencies of facilities serving in tourism.

Bifidobacterium infantis Metabolizes 2'Fucosyllactose-Derived and Free Fucose Through a Common Catabolic Pathway Resulting in 1,2-Propanediol Secretion.

Human milk oligosaccharides (HMOs) enrich beneficial bifidobacteria in the infant gut microbiome which produce molecules that impact development and physiology. 2'fucosyllactose (2'FL) is a highly abundant fucosylated HMO which is utilized by Bifidobacterium longum subsp. infantis, despite limited scientific understanding of the underlying mechanism. Moreover, there is not a current consensus on whether free fucose could be metabolized when not incorporated in a larger oligosaccharide structure. Based on metabolic and genomic analyses, we hypothesize that B. infantis catabolizes both free fucose and fucosyl oligosaccharide residues to produce 1,2-propanediol (1,2-PD). Accordingly, systems-level approaches including transcriptomics and proteomics support this metabolic path. Co-fermentation of fucose and limiting lactose or glucose was found to promote significantly higher biomass and 1,2-PD concentrations than individual substrates, suggesting a synergistic effect. In addition, and during growth on 2'FL, B. infantis achieves significantly higher biomass corresponding to increased 1,2-PD. These findings support a singular fucose catabolic pathway in B. infantis that is active on both free and HMO-derived fucose and intimately linked with central metabolism. The impact of fucose and 2'FL metabolism on B. infantis physiology provides insight into the role of fucosylated HMOs in influencing host- and microbe-microbe interactions within the infant gut microbiome.

COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease.

BACKGROUND: Data from the UK COVID-19 outbreak are emerging, and there are ongoing concerns about a disproportionate effect on ethnic minorities. There is very limited information on COVID-19 in the over-80s, and the rates of hospital-onset infections are unknown. METHODS: This was a retrospective cohort study from electronic case records of the first 450 patients admitted to our hospital with PCR-confirmed COVID-19, 77% of the total inpatient caseload to date. Demographic, clinical and biochemical data were extracted. The primary endpoint was death during the index hospital admission. The characteristics of all patients, those over 80 years of age and those with hospital-onset COVID-19 were examined. RESULTS: The median (IQR) age was 72 (56, 83), with 150 (33%) over 80 years old and 60% male. Presenting clinical and biochemical features were consistent with those reported elsewhere. The ethnic breakdown of patients admitted was similar to that of our underlying local population. Inpatient mortality was high at 38%. Patients over 80 presented earlier in their disease course and were significantly less likely to present with the typical features of cough, breathlessness and fever. Cardiac co-morbidity and markers of cardiac dysfunction were more common, but not those of bacterial infection. Mortality was significantly higher in this group (60% vs 28%, p < 0.001). Thirty-one (7%) patients acquired COVID-19 having continuously been in hospital for a median of 20 (14, 36) days. The peak of hospital-onset infections occurred at the same time as the overall peak of admitted infections. Despite being older and more frail than those with community-onset infection, their outcomes were no worse. CONCLUSIONS: Inpatient mortality was high, especially among the over-80s, who are more likely to present atypically. The ethnic composition of our caseload was similar to the underlying population. While a significant number of patients acquired COVID-19 while already in hospital, their outcomes were no worse.

Inefficient Metabolism of the Human Milk Oligosaccharides Lacto-N-tetraose and Lacto-N-neotetraose Shifts Bifidobacterium longum subsp. infantis Physiology.

Human milk contains a high concentration of indigestible oligosaccharides, which likely mediated the coevolution of the nursing infant with its gut microbiome. Specifically, Bifidobacterium longum subsp. infantis (B. infantis) often colonizes the infant gut and utilizes these human milk oligosaccharides (HMOs) to enrich their abundance. In this study, the physiology and mechanisms underlying B. infantis utilization of two HMO isomers lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) was investigated in addition to their carbohydrate constituents. Both LNT and LNnT utilization induced a significant shift in the ratio of secreted acetate to lactate (1.7-2.0) in contrast to the catabolism of their component carbohydrates (~1.5). Inefficient metabolism of LNnT prompts B. infantis to shunt carbon toward formic acid and ethanol secretion. The global transcriptome presents genomic features differentially expressed to catabolize these two HMO species that vary by a single glycosidic linkage. Furthermore, a measure of strain-level variation exists between B. infantis isolates. Regardless of strain, inefficient HMO metabolism induces the metabolic shift toward formic acid and ethanol production. Furthermore, bifidobacterial metabolites reduced LPS-induced inflammation in a cell culture model. Thus, differential metabolism of milk glycans potentially drives the emergent physiology of host-microbial interactions to impact infant health.

A Human Gut Commensal Ferments Cranberry Carbohydrates To Produce Formate.

Commensal bifidobacteria colonize the human gastrointestinal tract and catabolize glycans that are impervious to host digestion. Accordingly, Bifidobacterium longum typically secretes acetate and lactate as fermentative end products. This study tested the hypothesis that B. longum utilizes cranberry-derived xyloglucans in a strain-dependent manner. Interestingly, the B. longum strain that efficiently utilizes cranberry xyloglucans secretes 2.0 to 2.5 mol of acetate-lactate. The 1.5 acetate:lactate ratio theoretical yield obtained in hexose fermentations shifts during xyloglucan metabolism. Accordingly, this metabolic shift is characterized by increased acetate and formate production at the expense of lactate. α-l-Arabinofuranosidase, an arabinan endo-1,5-α-l-arabinosidase, and a ß-xylosidase with a carbohydrate substrate-binding protein and carbohydrate ABC transporter membrane proteins are upregulated (>2-fold change), which suggests carbon flux through this catabolic pathway. Finally, syntrophic interactions occurred with strains that utilize carbohydrate products derived from initial degradation from heterologous bacteria.IMPORTANCE This was a study of bacterial metabolism of complex cranberry carbohydrates termed xyloglucans that are likely not digested prior to reaching the colon. This is significant, as bifidobacteria interact with this dietary compound to potentially impact human host health through energy and metabolite production by utilizing these substrates. Specific bacterial strains utilize cranberry xyloglucans as a nutritive source, indicating unknown mechanisms that are not universal in bifidobacteria. In addition, xyloglucan metabolism proceeds by using an alternative pathway that could lead to further research to investigate mechanisms underlying this interaction. Finally, we observed cross-feeding between bacteria in which one strain degrades the cranberry xyloglucan to make it available to a second strain. Similar nutritive strategies are known to occur within the gut. In aggregate, this study may lead to novel foods or supplements used to impact human health through rational manipulation of the human microbiome.

Glycan cross-feeding activities between bifidobacteria under in vitro conditions.

Bifidobacteria colonize the gut of various mammals, including humans, where they may metabolize complex, diet-, and host-derived carbohydrates. The glycan-associated metabolic features encoded by bifidobacteria are believed to be strongly influenced by cross-feeding activities due to the co-existence of strains with different glycan-degrading properties. In this study, we observed an enhanced growth yield of Bifidobacterium bifidum PRL2010 when co-cultivated with Bifidobacterium breve 12L, Bifidobacterium adolescentis 22L, or Bifidobacterium thermophilum JCM1207. This enhanced growth phenomenon was confirmed by whole genome transcriptome analyses, which revealed co-cultivation-associated transcriptional induction of PRL2010 genes involved in carbohydrate metabolism, such as those encoding for carbohydrate transporters and associated energy production, and genes required for translation, ribosomal structure, and biogenesis, thus supporting the idea that co-cultivation of certain bifidobacterial strains with B. bifidum PRL2010 causes enhanced metabolic activity, and consequently increased lactate and/or acetate production. Overall, these data suggest that PRL2010 cells benefit from the presence of other bifidobacterial strains.