Gut-microbiota-targeted diets modulate human immune status.

Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.

Carbotoxicity-Noxious Effects of Carbohydrates.

Modern nutrition is often characterized by the excessive intake of different types of carbohydrates ranging from digestible polysaccharides to refined sugars that collectively mediate noxious effects on human health, a phenomenon that we refer to as "carbotoxicity." Epidemiological and experimental evidence combined with clinical intervention trials underscore the negative impact of excessive carbohydrate uptake, as well as the beneficial effects of reducing carbs in the diet. We discuss the molecular, cellular, and neuroendocrine mechanisms that link exaggerated carbohydrate intake to disease and accelerated aging as we outline dietary and pharmacologic strategies to combat carbotoxicity.

Control of immunity via nutritional interventions.

Nutrition affects all physiological processes including those linked to the development and function of our immune system. Here, we discuss recent evidence and emerging concepts supporting the idea that our newfound relationship with nutrition in industrialized countries has fundamentally altered the way in which our immune system is wired. This will be examined through the lens of studies showing that mild or transient reductions in dietary intake can enhance protective immunity while also limiting aberrant inflammatory responses. We will further discuss how trade-offs and priorities begin to emerge in the context of severe nutritional stress. In those settings, specific immunological functions are heightened to re-enforce processes and tissue sites most critical to survival. Altogether, these examples will emphasize the profound influence nutrition has over the immune system and highlight how a mechanistic exploration of this cross talk could ultimately lead to the design of novel therapeutic approaches that prevent and treat disease.

Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals.

Although food-directed immunoglobulin E (IgE) has been studied in the context of allergies, the prevalence and magnitude of IgG responses against dietary antigens are incompletely characterized in the general population. Here, we measured IgG binding against food and environmental antigens obtained from allergen databases and the immune epitope database (IEDB), represented in a phage displayed library of 58,233 peptides. By profiling blood samples of a large cohort representing the average adult Israeli population (n = 1,003), we showed that many food antigens elicited systemic IgG in up to 50% of individuals. Dietary intake of specific food protein correlated with antibody binding, suggesting that diet can shape the IgG epitope repertoire. Our work documents abundant systemic IgG responses against food antigens and provides a reference map of the exact immunogenic epitopes on a population scale, laying the foundation to unravel the role of food- and environmental antigen-directed antibody binding in disease contexts.

Translating energy balance research from the bench to the clinic to the community: Parallel animal-human studies in cancer.

Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer toward practice changes. This review summarizes key topics discussed to advance research on the role of energy balance, including physical activity, body composition, and dietary intake, on cancer development, cancer outcomes, and healthy survivorship.

Complex physiology and clinical implications of time-restricted eating.

Time-restricted eating (TRE) is a dietary intervention that limits food consumption to a specific time window each day. The effect of TRE on body weight and physiological functions has been extensively studied in rodent models, which have shown considerable therapeutic effects of TRE and important interactions among time of eating, circadian biology, and metabolic homeostasis. In contrast, it is difficult to make firm conclusions regarding the effect of TRE in people because of the heterogeneity in results, TRE regimens, and study populations. In this review, we 1) provide a background of the history of meal consumption in people and the normal physiology of eating and fasting; 2) discuss the interaction between circadian molecular metabolism and TRE; 3) integrate the results of preclinical and clinical studies that evaluated the effects of TRE on body weight and physiological functions; 4) summarize other time-related dietary interventions that have been studied in people; and 4) identify current gaps in knowledge and provide a framework for future research directions.

Deconstructing Mechanisms of Diet-Microbiome-Immune Interactions.

Emerging evidence suggests that the effect of dietary intake on human health and disease is linked to both the immune system and the microbiota. Yet, we lack an integrated mechanistic model for how these three complex systems relate, limiting our ability to understand and treat chronic and infectious disease. Here, we review recent findings at the interface of microbiology, immunology, and nutrition, with an emphasis on experimentally tractable models and hypothesis-driven mechanistic work. We outline emerging mechanistic concepts and generalizable approaches to bridge the gap between microbial ecology and molecular mechanism. These set the stage for a new era of precision human nutrition informed by a deep and comprehensive knowledge of the diverse cell types in and on the human body.

American Cancer Society nutrition and physical activity guideline for cancer survivors.

The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.

American Cancer Society guideline for diet and physical activity for cancer prevention.

The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.

Western diet influences on microbiome and carcinogenesis.

The intestinal microbiota composition and associated bioactivities are sensitive to various modifier cues such as stress, inflammation, age, life-style and nutrition, which in turn are associated with susceptibility to developing cancer. Among these modifiers, diet has been shown to influence both microbiota composition as well as being an important source of microbial-derived compounds impacting the immunological, neurological and hormonal systems. Thus, it is necessary to take a holistic view when considering effect of diet on health and diseases. In this review, we focus on the interplay between western diet, the microbiota and cancer development by dissecting key components of the diet and leveraging data from human interventions and pre-clinical studies to better understand this relationship. We highlight key progress as well as stressing limitations in this field of research.

Meta-analysis and public policy: Reconciling the evidence on deworming.

The WHO recommends mass drug administration (MDA) for intestinal worm infections in areas with over 20% infection prevalence. Recent Cochrane meta-analyses endorse treatment of infected individuals but recommend against MDA. We conducted a theory-agnostic random-effects meta-analysis of the effect of multiple-dose MDA and a cost-effectiveness analysis. We estimate significant effects of MDA on child weight (0.15 kg, 95% CI: 0.07, 0.24; P < 0.001), mid-upper arm circumference (0.20 cm, 95% CI: 0.03, 0.37; P = 0.02), and height (0.09 cm, 95% CI: 0.01, 0.16; P = 0.02) when prevalence is over 20% but not on Hb (0.06 g/dL, 95% CI: -0.01, 0.14; P = 0.1). These results suggest that MDA is a cost-effective intervention, particularly in the settings where it is recommended by the WHO.

Characterizing pathways of seafood access in small island developing states.

Ensuring healthy and sustainable food systems in increasing social, economic, and ecological change is a key global priority to protect human and environmental health. Seafood is an essential component of these food systems and a critical source of nutrients, especially in coastal communities. However, despite rapid transformations in aquatic food systems, and our urgent need to understand them, there is a dearth of data connecting harvested food production to actualized food consumption. Many analyses suggest institutional, legal, or technological innovations to improve food systems, but few have analyzed the pathways through which people already gain access to nutritious food. Here, using a random forest model and cluster analysis of a nationally representative data set from Kiribati, we operationalize access theory to trace the flows of consumptive benefit in a fisheries-based food system. We demonstrate that the market access mechanism is the key mechanism mediating seafood access in Kiribati, but importantly, the highest seafood consumption households showed lower market access, pointing to the importance of non-market acquisition (e.g., home production and gifting). We reveal six distinct household strategies that employ different sets of access mechanisms to ensure high levels of local seafood consumption in different contexts. We demonstrate the impacts of these strategies on the composition of household seafoods consumed, stressing the need to support these existing successful strategies. Finally, we point to key policy and management insights (e.g., improved infrastructure, shifts in species management) that may be more effective in reinforcing these existing pathways than commonly proposed food system interventions.

Commercially traded fish portfolios mask household utilization of biodiversity in wild food systems.

The global biodiversity that underpins wild food systems-including fisheries-is rapidly declining. Yet, we often have only a limited understanding of how households use and benefit from biodiversity in the ecosystems surrounding them. Explicating these relationships is critical to forestall and mitigate the effects of biodiversity declines on food and nutrition security. Here, we quantify how biodiversity filters from ecosystems to household harvest, consumption, and sale, and how ecological traits and household characteristics shape these relationships. We used a unique, integrated ecological (40 sites, quarterly data collection) and household survey (n = 414, every 2 mo data collection) dataset collected over 3 y in rice field fisheries surrounding Cambodia's Tonlé Sap, one of Earth's most productive and diverse freshwater systems. While ecosystem biodiversity was positively associated with household catch, consumption, and sold biodiversity, households consumed an average of 43% of the species present in the ecosystem and sold only 9%. Larger, less nutritious, and more common species were disproportionally represented in portfolios of commercially traded species, while consumed species mirrored catches. The relationship between ecosystem and consumed biodiversity was remarkably consistent across variation in household fishing effort, demographics, and distance to nearest markets. Poorer households also consumed more species, underscoring how wild food systems may most benefit the vulnerable. Our findings amplify concerns about the impacts of biodiversity loss on our global food systems and highlight that utilization of biodiversity for consumption may far exceed what is commercially traded.

The Role of the Gut Microbiota in the Relationship Between Diet and Human Health.

The interplay between diet, the gut microbiome, and host health is complex. Diets associated with health have many similarities: high fiber, unsaturated fatty acids, and polyphenols while being low in saturated fats, sodium, and refined carbohydrates. Over the past several decades, dietary patterns have changed significantly in Westernized nations with the increased consumption of calorically dense ultraprocessed foods low in fiber and high in saturated fats, salt, and refined carbohydrates, leading to numerous negative health consequences including obesity, metabolic syndrome, and cardiovascular disease. The gut microbiota is an environmental factor that interacts with diet and may also have an impact on health outcomes, many of which involve metabolites produced by the microbiota from dietary components that can impact the host. This review focuses on our current understanding of the complex relationship between diet, the gut microbiota, and host health, with examples of how diet can support health, increase an individual's risk for disease, and be used as a therapy for specific diseases.

Nutritional control of developmental processes.

Nutritional and metabolic cues are integral to animal development. Organisms use them both as sustenance and environmental indicators, fueling, informing and influencing developmental decisions. Classical examples, such as the Warburg effect, clearly illustrate how genetic programs control metabolic changes. However, the way that nutrition and metabolism can also modulate or drive genetic programs to instruct developmental trajectories is much more elusive, owing to several difficulties including uncoupling permissive and instructive functions. Here, we discuss recent advancements in the field that highlight the developmental role of nutritional and metabolic cues across multiple levels of organismal complexity.

A predatory gastrula leads to symbiosis-independent settlement in Aiptasia.

The planula larvae of the sea anemone Aiptasia have so far not been reported to complete their life cycle by undergoing metamorphosis into adult forms. This has been a major obstacle in their use as a model for coral-dinoflagellate endosymbiosis. Here, we show that Aiptasia larvae actively feed on crustacean nauplii, displaying a preference for live prey. This feeding behavior relies on functional stinging cells, indicative of complex neuronal control. Regular feeding leads to significant size increase, morphological changes, and efficient settlement around 14 d postfertilization. Surprisingly, the presence of dinoflagellate endosymbionts does not affect larval growth or settlement dynamics but is crucial for sexual reproduction. Our findings finally close Aiptasia's life cycle and highlight the functional nature of its larvae, as in Haeckel's Gastrea postulate, yet reveal its active carnivory, thus contributing to our understanding of early metazoan evolution.

Microbiota configuration determines nutritional immune optimization.

Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we propose that DR-induced optimization of immunological memory requires a complex cascade of events involving memory T cells, the intestinal microbiota, and myeloid cells. Our findings suggest that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes the expansion of commensal Bifidobacteria within the large intestine, which produce the short-chain fatty acid acetate. Acetate conditioning of the myeloid compartment during DR enhances the capacity of these cells to kill pathogens. Enhanced host protection during DR is compromised when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function play an important role in determining immune responsiveness to this dietary intervention. Altogether, our study supports the idea that DR induces both memory T cells and the gut microbiota to produce distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings suggest that nutritional cues can promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.

Forgotten food crops in sub-Saharan Africa for healthy diets in a changing climate.

As climate changes in sub-Saharan Africa (SSA), Africa's "forgotten" food crops offer a wide range of options to diversify major staple production as a key measure toward achieving zero hunger and healthy diets. So far, however, these forgotten food crops have been neglected in SSA's climate-change adaptation strategies. Here, we quantified their capacity to adapt cropping systems of SSA's major staples of maize, rice, cassava, and yams to changing climates for the four subregions of West, Central, East, and Southern Africa. We used climate-niche modeling to explore their potential for crop diversification or the replacement of these major staples by 2070, and assessed the possible effects on micronutrient supply. Our results indicated that approximately 10% of the present production locations of these four major staples in SSA may experience novel climate conditions in 2070, ranging from a high of almost 18% in West Africa to a low of less than 1% in Southern Africa. From an initial candidate panel of 138 African forgotten food crops embracing leafy vegetables, other vegetables, fruits, cereals, pulses, seeds and nuts, and roots and tubers, we selected those that contributed most to covering projected future and contemporary climate conditions of the major staples' production locations. A prioritized shortlist of 58 forgotten food crops, able to complement each other in micronutrient provision, was determined, which covered over 95% of assessed production locations. The integration of these prioritized forgotten food crops in SSA's cropping systems will support the "double-win" of more climate-resilient and nutrient-sensitive food production in the region.

Diversity of plant DNA in stool is linked to dietary quality, age, and household income.

Eating a varied diet is a central tenet of good nutrition. Here, we develop a molecular tool to quantify human dietary plant diversity by applying DNA metabarcoding with the chloroplast trnL-P6 marker to 1,029 fecal samples from 324 participants across two interventional feeding studies and three observational cohorts. The number of plant taxa per sample (plant metabarcoding richness or pMR) correlated with recorded intakes in interventional diets and with indices calculated from a food frequency questionnaire in typical diets (ρ = 0.40 to 0.63). In adolescents unable to collect validated dietary survey data, trnL metabarcoding detected 111 plant taxa, with 86 consumed by more than one individual and four (wheat, chocolate, corn, and potato family) consumed by >70% of individuals. Adolescent pMR was associated with age and household income, replicating prior epidemiologic findings. Overall, trnL metabarcoding promises an objective and accurate measure of the number and types of plants consumed that is applicable to diverse human populations.

Role of the intestinal microbiota in contributing to weight disorders and associated comorbidities.

SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.