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Modernization of society from a rural, hunter-gatherer setting into an urban and industrial one, with the associated dietary changes, has led to an increased prevalence of cardiometabolic and additional noncommunicable diseases, such as cancer, inflammatory bowel disease, and neurodegenerative and autoimmune disorders. However, while dietary sciences have been rapidly evolving to meet these challenges, validation and translation of experimental results into clinical practice remain limited for multiple reasons, including inherent ethnic, gender, and cultural interindividual variability, among other methodological, dietary reporting–related, and analytical issues. Recently, large clinical cohorts with artificial intelligence analytics have introduced new precision and personalized nutrition concepts that enable one to successfully bridge these gaps in a real-life setting. In this review, we highlight selected examples of case studies at the intersection between diet–disease research and artificial intelligence. We discuss their potential and challenges and offer an outlook toward the transformation of dietary sciences into individualized clinical translation. Expected final online publication date for the Annual Review of Nutrition, Volume 43 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses. We causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.

We report the results of a first exploratory study testing the use of vaginal microbiome transplantation (VMT) from healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and recurrent bacterial vaginosis (ClinicalTrials.gov NCT02236429 ). In our case series, five patients were treated, and in four of them VMT was associated with full long-term remission until the end of follow-up at 5-21 months after VMT, defined as marked improvement of symptoms, Amsel criteria, microscopic vaginal fluid appearance and reconstitution of a Lactobacillus-dominated vaginal microbiome. One patient presented with incomplete remission in clinical and laboratory features. No adverse effects were observed in any of the five women. Notably, remission in three patients necessitated repeated VMT, including a donor change in one patient, to elicit a long-standing clinical response. The therapeutic efficacy of VMT in women with intractable and recurrent bacterial vaginosis should be further determined in randomized, placebo-controlled clinical trials.

Summary Machine learning is increasingly integrated into clinical practice, with applications ranging from pre-clinical data processing, bedside diagnosis assistance, patient stratification, treatment decision making, and early warning as part of primary and secondary prevention. However, a multitude of technological, medical, and ethical considerations are critical in machine-learning utilization, including the necessity for careful validation of machine-learning-based technologies in real-life contexts, unbiased evaluation of benefits and risks, and avoidance of technological over-dependence and associated loss of clinical, ethical, and social-related decision-making capacities. Other challenges include the need for careful benchmarking and external validations, dissemination of end-user knowledge from computational experts to field users, and responsible code and data sharing, enabling transparent assessment of pipelines. In this review, we highlight key promises and achievements in integration of machine-learning platforms into clinical medicine while highlighting limitations, pitfalls, and challenges toward enhanced integration of learning systems into the medical realm.

Cigarette smoking constitutes a leading global cause of morbidity and preventable death

Studies of galaxy surveys in the context of the cold dark matter paradigm have shown that the mass of the dark matter halo and the total stellar mass are coupled through a function that varies smoothly with mass. Their average ratio M_{halo}/M_{stars} has a minimum of about 30 for galaxies with stellar masses near that of the Milky Way (approximately 5x10^{10} solar masses) and increases both towards lower masses and towards higher masses. The scatter in this relation is not well known; it is generally thought to be less than a factor of two for massive galaxies but much larger for dwarf galaxies. Here we report the radial velocities of ten luminous globular-cluster-like objects in the ultra-diffuse galaxy NGC1052-DF2, which has a stellar mass of approximately 2x10^8 solar masses. We infer that its velocity dispersion is less than 10.5 kilometers per second with 90 per cent confidence, and we determine from this that its total mass within a radius of 7.6 kiloparsecs is less than 3.4x10^8 solar masses. This implies that the ratio M_{halo}/M_{stars} is of order unity (and consistent with zero), a factor of at least 400 lower than expected. NGC1052-DF2 demonstrates that dark matter is not always coupled with baryonic matter on galactic scales., Comment: To appear in the 29 March issue of Nature

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder, in which the clinical manifestations may be influenced by genetic and unknown environmental factors. Here we show that ALS-prone Sod1 transgenic (Sod1-Tg) mice have a pre-symptomatic, vivarium-dependent dysbiosis and altered metabolite configuration, coupled with an exacerbated disease under germ-free conditions or after treatment with broad-spectrum antibiotics. We correlate eleven distinct commensal bacteria at our vivarium with the severity of ALS in mice, and by their individual supplementation into antibiotic-treated Sod1-Tg mice we demonstrate that Akkermansia muciniphila (AM) ameliorates whereas Ruminococcus torques and Parabacteroides distasonis exacerbate the symptoms of ALS. Furthermore, Sod1-Tg mice that are administered AM are found to accumulate AM-associated nicotinamide in the central nervous system, and systemic supplementation of nicotinamide improves motor symptoms and gene expression patterns in the spinal cord of Sod1-Tg mice. In humans, we identify distinct microbiome and metabolite configurations-including reduced levels of nicotinamide systemically and in the cerebrospinal fluid-in a small preliminary study that compares patients with ALS with household controls. We suggest that environmentally driven microbiome-brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.

We report the results of a first exploratory study testing the use of vaginal microbiome transplantation (VMT) from healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and recurrent bacterial vaginosis (ClinicalTrials.gov NCT02236429 ). In our case series, five patients were treated, and in four of them VMT was associated with full long-term remission until the end of follow-up at 5-21 months after VMT, defined as marked improvement of symptoms, Amsel criteria, microscopic vaginal fluid appearance and reconstitution of a Lactobacillus-dominated vaginal microbiome. One patient presented with incomplete remission in clinical and laboratory features. No adverse effects were observed in any of the five women. Notably, remission in three patients necessitated repeated VMT, including a donor change in one patient, to elicit a long-standing clinical response. The therapeutic efficacy of VMT in women with intractable and recurrent bacterial vaginosis should be further determined in randomized, placebo-controlled clinical trials.

Throughout a 24-h period, the small intestine (SI) is exposed to diurnally varying food- and microbiome-derived antigenic burdens but maintains a strict immune homeostasis, which when perturbed in genetically susceptible individuals, may lead to Crohn disease. Herein, we demonstrate that dietary content and rhythmicity regulate the diurnally shifting SI epithelial cell (SIEC) transcriptional landscape through modulation of the SI microbiome. We exemplify this concept with SIEC major histocompatibility complex (MHC) class II, which is diurnally modulated by distinct mucosal-adherent SI commensals, while supporting downstream diurnal activity of intra-epithelial IL-10+ lymphocytes regulating the SI barrier function. Disruption of this diurnally regulated diet-microbiome-MHC class II-IL-10-epithelial barrier axis by circadian clock disarrangement, alterations in feeding time or content, or epithelial-specific MHC class II depletion leads to an extensive microbial product influx, driving Crohn-like enteritis. Collectively, we highlight nutritional features that modulate SI microbiome, immunity, and barrier function and identify dietary, epithelial, and immune checkpoints along this axis to be potentially exploitable in future Crohn disease interventions.

We present HST/ACS imaging of twenty-three very low surface brightness ($��_{e,V}$=25-27.5) galaxies detected in the fields of four nearby galaxy groups. These objects were selected from deep optical imaging obtained with the Dragonfly Telephoto Array. Seven are new discoveries, while most of the others had been identified previously in visual surveys of deep photographic plates and more recent surveys. Few have previously been studied in detail. From the ACS images, we measure distances to the galaxies using both the tip of the red giant branch method and the surface brightness fluctuations method. We demonstrate that the two methods are consistent with each other in the regime where both can be applied. The distances to 15 out of 20 galaxies with stable measurements are consistent with that of the targeted group within errors. This suggests that assuming group membership based solely on projected proximity is ~75% successful in this regime. The galaxies are nearly round, with a median axis ratio of 0.85, and visually resemble dwarf spheroidal galaxies. The objects have a range of sizes, from $R_e$=0.4 kpc to $R_e$=1.8 kpc, with a median of 1.0 kpc. They range in luminosity from $M_V$=-11.4 to $M_V$=-15.6, with a median of -12.4. Galaxies with $R_e$~1 kpc and $M_V$~-12 are fairly rare in the Local Group but we find many of them in this relatively small sample. Four of the objects fall in the class of ultra diffuse galaxies (UDGs), with $R_e$>1.5 kpc and $��_{0,V}$>24 mag/arcsec^2, including the recently identified dark matter deficient galaxy NGC1052-DF2., Submitted to ApJ. All reduced HST images are available upon request

We report tentative evidence for a cold stellar stream in the ultra-diffuse galaxy NGC1052-DF2. If confirmed, this stream (which we refer to as "The Maybe Stream") would be the first cold stellar stream detected outside of the Local Group. The candidate stream is very narrow and has an unusual and highly curved shape., Accepted for publication in RNAAS

We recently inferred that the galaxy NGC1052-DF2 has little or no dark matter and a rich system of unusual globular clusters. We assumed that the galaxy is a satellite of the luminous elliptical galaxy NGC1052 at ~20 Mpc, on the basis of its surface brightness fluctuations (SBF) distance of $19.0 \pm 1.7$ Mpc, its radial velocity of ~1800 km/s, and its projected position. Here we analyze the color-magnitude diagram (CMD) of NGC1052-DF2, following the suggestion by Trujillo et al. (2018) that the tip of the red giant branch (TRGB) can be detected in currently available HST data and the galaxy is at ~13 Mpc. Using fully populated galaxy models we show that the CMD is strongly influenced by blends. These blends produce a "phantom" TRGB ~2 times brighter than the true TRGB, which can lead to erroneous distance estimates ~1.4 times smaller than the actual distance. We compare NGC1052-DF2 to model images as well as other galaxies in our HST sample, and show that the large population of unblended RGB stars expected for distances of ~13 Mpc is not detected. We also provide a new distance measurement to NGC1052-DF2 that is free of calibration uncertainties, by anchoring it to a satellite of the megamaser host galaxy NGC4258. From a megamaser-TRGB-SBF distance ladder we obtain $D=18.7 \pm 1.7$ Mpc, consistent with our previous measurement and with the distance to the elliptical galaxy NGC1052., Comment: Accepted for publication in ApJ Letters. The key point of the paper is made in Figure 2. All data and models are available upon request. Minor changes compared to V1 make the paper more of a stand-alone analysis and less of a response to Trujillo et al. (2018). Also see the independent analysis of Blakeslee & Cantiello (arXiv:1808.02176)

We recently published velocity measurements of luminous globular clusters in the galaxy NGC1052-DF2, concluding that it lies far off the canonical stellar mass - halo mass relation. Here we present a revised velocity for one of the globular clusters, GC-98, and a revised velocity dispersion measurement for the galaxy. We find that the intrinsic dispersion $\sigma=5.6^{+5.2}_{-3.8}$ km/s using Approximate Bayesian Computation, or $\sigma=7.8^{+5.2}_{-2.2}$ km/s using the likelihood. The expected dispersion from the stars alone is ~7 km/s. Responding to a request from the Editors of ApJ Letters and RNAAS, we also briefly comment on the recent analysis of our measurements by Martin et al. (2018)., Comment: Published in the Research Notes of the AAS. 2 pages, 1 figure

The discovery of the ultra-diffuse galaxy NGC 1052-DF2 and its peculiar population of star clusters has raised new questions about the connections between galaxies and dark matter halos at the extremes of galaxy formation. In light of debates over the measured velocity dispersion of its star clusters and the associated mass estimate, we constrain mass models of DF2 using its observed kinematics with a range of priors on the halo mass. Models in which the galaxy obeys a standard stellar-halo mass relation are in tension with the data and also require a large central density core. Better fits are obtained when the halo mass is left free, even after accounting for increased model complexity. The dynamical mass-to-light ratio for our model with a weak prior on the halo mass is $1.7^{+0.7}_{-0.5} \ M_\odot / L_{\odot, V}$, consistent with the stellar population estimate for DF2. We use tidal analysis to find that the low-mass models are consistent with the undisturbed isophotes of DF2. Finally we compare with Local Group dwarf galaxies and demonstrate that DF2 is an outlier in both its spatial extent and its relative dark matter deficit., Comment: accepted to ApJL, 9 pages, 4 figures

Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.

Probiotics are widely prescribed for prevention of antibiotics-associated dysbiosis and related adverse effects. However, probiotic impact on post-antibiotic reconstitution of the gut mucosal host-microbiome niche remains elusive. We invasively examined the effects of multi-strain probiotics or autologous fecal microbiome transplantation (aFMT) on post-antibiotic reconstitution of the murine and human mucosal microbiome niche. Contrary to homeostasis, antibiotic perturbation enhanced probiotics colonization in the human mucosa but only mildly improved colonization in mice. Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and persistently incomplete indigenous stool/mucosal microbiome reconstitution and host transcriptome recovery toward homeostatic configuration, while aFMT induced a rapid and near-complete recovery within days of administration. In vitro, Lactobacillus-secreted soluble factors contributed to probiotics-induced microbiome inhibition. Collectively, potential post-antibiotic probiotic benefits may be offset by a compromised gut mucosal recovery, highlighting a need of developing aFMT or personalized probiotic approaches achieving mucosal protection without compromising microbiome recolonization in the antibiotics-perturbed host.

We recently found an ultra diffuse galaxy (UDG) with a half-light radius of R_e = 2.2 kpc and little or no dark matter. The total mass of NGC1052-DF2 was measured from the radial velocities of bright compact objects that are associated with the galaxy. Here we analyze these objects using a combination of HST imaging and Keck spectroscopy. Their average size is = 6.2+-0.5 pc and their average ellipticity is = 0.18+-0.02. From a stacked Keck spectrum we derive an age >9 Gyr and a metallicity of [Fe/H] = -1.35+-0.12. Their properties are similar to {\omega} Centauri, the brightest and largest globular cluster in the Milky Way, and our results demonstrate that the luminosity function of metal-poor globular clusters is not universal. The fraction of the total stellar mass that is in the globular cluster system is similar to that in other UDGs, and consistent with "failed galaxy" scenarios where star formation terminated shortly after the clusters were formed. However, the galaxy is a factor of ~1000 removed from the relation between globular cluster mass and total galaxy mass that has been found for other galaxies, including other UDGs. We infer that a dark matter halo is not a prerequisite for the formation of metal-poor globular cluster-like objects in high redshift galaxies., Comment: Accepted for publication in ApJ Letters