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Short- and Long-Term Implications of Human Milk Microbiota on Maternal and Child Health.
García-Ricobaraza, M, García-Santos, JA, Escudero-Marín, M, Diéguez, E, Cerdó, T, Campoy, C
International journal of molecular sciences. 2021;(21)
Abstract
Human milk (HM) is considered the most complete food for infants as its nutritional composition is specifically designed to meet infant nutritional requirements during early life. HM also provides numerous biologically active components, such as polyunsaturated fatty acids, milk fat globules, IgA, gangliosides or polyamines, among others; in addition, HM has a "bifidogenic effect", a prebiotic effect, as a result of the low concentration of proteins and phosphates, as well as the presence of lactoferrin, lactose, nucleotides and oligosaccharides. Recently, has been a growing interest in HM as a potential source of probiotics and commensal bacteria to the infant gut, which might, in turn, influence both the gut colonization and maturation of infant immune system. Our review aims to address practical approaches to the detection of microbial communities in human breast milk samples, delving into their origin, composition and functions. Furthermore, we will summarize the current knowledge of how HM microbiota dysbiosis acts as a short- and long-term predictor of maternal and infant health. Finally, we also provide a critical view of the role of breast milk-related bacteria as a novel probiotic strategy in the prevention and treatment of maternal and offspring diseases.
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Microbiota, Bacterial Carbonic Anhydrases, and Modulators of Their Activity: Links to Human Diseases?
Amedei, A, Capasso, C, Nannini, G, Supuran, CT
Mediators of inflammation. 2021;:6926082
Abstract
The involvement of the human microbiome is crucial for different host functions such as protection, metabolism, reproduction, and especially immunity. However, both endogenous and exogenous factors can affect the balance of the microbiota, creating a state of dysbiosis, which can start various gastrointestinal or systemic diseases. The challenge of future medicine is to remodel the intestinal microbiota to bring it back to healthy equilibrium (eubiosis) and, thus, counteract its negative role in the diseases' onset. The shaping of the microbiota is currently practiced in different ways ranging from diet (or use of prebiotics, probiotics, and synbiotics) to phage therapy and antibiotics, including microbiota fecal transplantation. Furthermore, because microbiota modulation is a capillary process, and because many microbiota bacteria (both beneficial and pathogenic) have carbonic anhydrases (specifically the four classes α, β, γ, and ι), we believe that the use of CA inhibitors and activators can open up new therapeutic strategies for many diseases associated with microbial dysbiosis, such as the various gastrointestinal disorders and the same colorectal cancer.
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Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy.
Gonciarz, RL, Renslo, AR
Current opinion in chemical biology. 2021;:170-178
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Abstract
Chemical tools capable of detecting ferrous iron with oxidation-state specificity have only recently become available. Coincident with this development in chemical biology has been increased study and appreciation for the importance of ferrous iron during infection and more generally in host-pathogen interaction. Some of the recent findings are surprising and challenge long-standing assumptions about bacterial iron homeostasis and the innate immune response to infection. Here, we review these recent developments and their implications for antibacterial therapy.
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Human Milk Microbiota and Oligosaccharides: A Glimpse into Benefits, Diversity, and Correlations.
Moubareck, CA
Nutrients. 2021;(4)
Abstract
Human milk represents a cornerstone for growth and development of infants, with extensive array of benefits. In addition to exceptionally nutritive and bioactive components, human milk encompasses a complex community of signature bacteria that helps establish infant gut microbiota, contributes to maturation of infant immune system, and competitively interferes with pathogens. Among bioactive constituents of milk, human milk oligosaccharides (HMOs) are particularly significant. These are non-digestible carbohydrates forming the third largest solid component in human milk. Valuable effects of HMOs include shaping intestinal microbiota, imparting antimicrobial effects, developing intestinal barrier, and modulating immune response. Moreover, recent investigations suggest correlations between HMOs and milk microbiota, with complex links possibly existing with environmental factors, genetics, geographical location, and other factors. In this review, and from a physiological and health implications perspective, milk benefits for newborns and mothers are highlighted. From a microbiological perspective, a focused insight into milk microbiota, including origins, diversity, benefits, and effect of maternal diet is presented. From a metabolic perspective, biochemical, physiological, and genetic significance of HMOs, and their probable relations to milk microbiota, are addressed. Ongoing research into mechanistic processes through which the rich biological assets of milk promote development, shaping of microbiota, and immunity is tackled.
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Evidence for maternal diet-mediated effects on the offspring microbiome and immunity: implications for public health initiatives.
Mirpuri, J
Pediatric research. 2021;(2):301-306
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Abstract
Diets rich in saturated fats have become a staple globally. Fifty percent of women of childbearing age in the United States are obese or overweight, with diet being a significant contributor. There is increasing evidence of the impact of maternal high-fat diet on the offspring microbiome. Alterations of the neonatal microbiome have been shown to be associated with multiple morbidities, including the development of necrotizing enterocolitis, atopy, asthma, metabolic dysfunction, and hypertension among others. This review provides an overview of the recent studies and mechanisms being examined on how maternal diet can alter the immune response and microbiome in offspring and the implications for directed public health initiatives for women of childbearing age. IMPACT Maternal diet is important in shaping the offspring microbiome and neonatal immune system. Reviews the current literature in the field and suggests potential mechanisms and areas of research to be targeted. Highlights the current scope of our knowledge of ideal nutrition during pregnancy and consideration for enhanced public health initiatives to promote well-being of the future generation.
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Human guanylate binding proteins: nanomachines orchestrating host defense.
Kutsch, M, Coers, J
The FEBS journal. 2021;(20):5826-5849
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Abstract
Disease-causing microorganisms not only breach anatomical barriers and invade tissues but also frequently enter host cells, nutrient-enriched environments amenable to support parasitic microbial growth. Protection from many infectious diseases is therefore reliant on the ability of individual host cells to combat intracellular infections through the execution of cell-autonomous defense programs. Central players in human cell-autonomous immunity are members of the family of dynamin-related guanylate binding proteins (GBPs). The importance of these interferon-inducible GTPases in host defense to viral, bacterial, and protozoan pathogens has been established for some time; only recently, cell biological and biochemical studies that largely focused on the prenylated paralogs GBP1, GBP2, and GBP5 have provided us with robust molecular frameworks for GBP-mediated immunity. Specifically, the recent characterization of GBP1 as a bona fide pattern recognition receptor for bacterial lipopolysaccharide (LPS) disrupting the integrity of bacterial outer membranes through LPS aggregation, the discovery of a link between hydrolysis-induced GMP production by GBP1 and inflammasome activation, and the classification of GBP2 and GBP5 as inhibitors of viral envelope glycoprotein processing via suppression of the host endoprotease furin have paved the way for a vastly improved conceptual understanding of the molecular mechanisms by which GBP nanomachines execute cell-autonomous immunity. The herein discussed models incorporate our current knowledge of the antimicrobial, proinflammatory, and biochemical properties of human GBPs and thereby provide testable hypotheses that will guide future studies into the intricacies of GBP-controlled host defense and their role in human disease.
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Bacterial Responses to Iron Withholding by Calprotectin.
Obisesan, AO, Zygiel, EM, Nolan, EM
Biochemistry. 2021;(45):3337-3346
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Abstract
Iron (Fe) plays important roles in both essential cellular processes and virulence pathways for many bacteria. Consequently, Fe withholding by the human innate immune system is an effective form of defense against bacterial infection. In this Perspective, we review recent studies that have established a foundation for our understanding of the impact of the metal-sequestering host defense protein calprotectin (CP) on bacterial Fe homeostasis. We also discuss two recently uncovered strategies for bacterial adaptation to Fe withholding by CP. Together, these studies provide insight into how Fe sequestration by CP affects bacterial pathogens that include Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Overall, recent studies suggest that Fe withholding by CP may have implications for bacterial survival and virulence in the host, and further explorations that directly address this possibility present an important area for discovery.
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Effects of short chain fatty acids on metabolic and inflammatory processes in human health.
Campos-Perez, W, Martinez-Lopez, E
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2021;(5):158900
Abstract
Butyrate, propionate, and acetate are short-chain fatty acids (SCFAs) mainly produced by bacterial metabolism in the human gut after dietary fiber intake. SCFAs are considered important for health maintenance by promoting lipid, glucose, and immune homeostasis with an adequate composition of intestinal microbiota, including other beneficial effects like providing protection against colorectal cancer. Therapies with exogenous SCFAs have been proposed to reduce inflammation in intestinal diseases that result from SCFA dysbiosis and cause mucosal inflammation. The aim of this mini-review was to provide an overview of the importance of SCFAs on metabolic and inflammatory processes as well as their role in treating chronic inflammatory disorders.
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The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health.
Nogal, A, Valdes, AM, Menni, C
Gut microbes. 2021;(1):1-24
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Abstract
The gut microbiota plays an important role in cardio-metabolic diseases with diet being among the strongest modulators of gut microbiota composition and function. Resistant dietary carbohydrates are fermented to short-chain fatty acids (SCFAs) by the gut bacteria. Fiber and omega-3 rich diets increase SCFAs production and abundance of SCFA-producing bacteria. Likewise, SCFAs can improve gut barrier integrity, glucose, and lipid metabolism, regulate the immune system, the inflammatory response, and blood pressure. Therefore, targeting the gut microbiota with dietary strategies leading to increased SCFA production may benefit cardio-metabolic health. In this review, we provide an overview of the association between diet, SCFAs produced by the gut microbiota and cardio-metabolic diseases. We first discuss the association between the human gut microbiota and cardio-metabolic diseases, then investigate the role of SCFAs and finally explore the beneficial effects of specific dietary interventions that can improve cardio-metabolic outcomes through boosting the SCFA production.
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Production of Psychoactive Metabolites by Gut Bacteria.
Wiley, NC, Cryan, JF, Dinan, TG, Ross, RP, Stanton, C
Modern trends in psychiatry. 2021;:74-99
Abstract
The gut microbiome plays a vital role in numerous aspects of physiology, including functions related to metabolism, the immune system, behaviour, brain structure and function. Furthermore, it is now becoming increasingly clear that alterations in microbial composition or diversity are implicated in several disease states, including anxiety, depression, autism spectrum disorder (ASD), Alzheimer's disease (AD), Parkinson's disease (PD), obesity, and diabetes. Therefore, therapeutic targeting of the gut microbiota has the potential to be useful in the treatment of both stress-related disorders and metabolic diseases. An important method by which the gut microbiome can influence the gut-brain axis is through microbial production of psychoactive metabolites. Several bacteria have been shown to produce metabolites which can impact host health, such as short-chain fatty acids, conjugated linoleic acid, antimicrobials, exopolysaccharides, and vitamins. Furthermore, several molecules with neuroactive functions, including serotonin, gamma-aminobutyric acid, catecholamines, and acetylcholine, have been isolated from bacteria within the human gut. This review aims to explore the psychoactive metabolites reported to be produced by gut bacteria, particularly those of relevance to stress-related disorders. Screening methods for psychoactive metabolite production, as well as the challenges and limitations of this research, will also be addressed. Finally, the implications of metabolite production for neuropsychiatric disorders such as depression, anxiety, and stress, behavioural disorders such as ASD, and neurodegenerative disorders such as AD and PD will be discussed.