Intestinal Dysbiosis in the Infant and the Future of Lacto-Engineering to Shape the Developing Intestinal Microbiome

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.

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The Role of Fusobacterium nucleatum in Colorectal Carcinogenesis

Pathobiology ◽

10.1159/000512175 ◽

2020 ◽

pp. 1-14

Author(s):

José Guilherme Datorre ◽

Ana Carolina de Carvalho ◽

Denise Peixoto Guimarães ◽

Rui Manuel Reis

Keyword(s):

Clinical Utility ◽

Therapy Response ◽

Fusobacterium Nucleatum ◽

Colorectal Carcinogenesis ◽

Intestinal Microbiome ◽

Bacterial Strains ◽

Molecular Features ◽

Important Target ◽

Intestinal Dysbiosis

Colorectal cancer (CRC) is one of the most frequent and deadly neoplasms worldwide. Genetic factors, lifestyle habits, and inflammation are important risk factors associated with CRC development. In recent years, growing evidence has supporting the significant role of the intestinal microbiome in CRC carcinogenesis. Disturbances in the healthy microbial balance, known as dysbiosis, are frequently observed in these patients. Pathogenic microorganisms that induce intestinal dysbiosis have become an important target to determine the role of bacterial infection in tumorigenesis. Interestingly, the presence of different bacterial strains, such as Fusobacterium nucleatum, has been detected in tissue and stool from patients with CRC and associated with substantial clinical and molecular features, as well as with patient therapy response. Therefore, understanding how the presence and levels of F. nucleatumstrains in the gut affect the risk of CRC onset and progression may inform suitable candidates for interventions focused on modulation of this bacteria. Here we review new insights into the role of gut microbiota in CRC carcinogenesis and the clinical utility of using the detection of F. nucleatum in different settings such as screening, prognosis, and microbiota modulation as a means to prevent cancer, augment therapies, and reduce adverse effects of treatment.

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Impact of Early Life Antibiotic Exposure and Neonatal Hyperoxia on the Murine Microbiome and Lung Injury

Scientific Reports ◽

10.1038/s41598-019-51506-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Melissa H. Althouse ◽

Christopher Stewart ◽

Weiwu Jiang ◽

Bhagavatula Moorthy ◽

Krithika Lingappan

Keyword(s):

Lung Injury ◽

Beta Diversity ◽

Alpha Diversity ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Antibiotic Exposure ◽

Neonatal Mice ◽

Intestinal Dysbiosis ◽

Neonatal Hyperoxia

Abstract Cross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.

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Antibiotic treatment in infants: effect on the gastro-intestinal microbiome and long term consequences

World Nutrition Journal ◽

10.25220/wnj/v02.i1.0003 ◽

2018 ◽

Vol 2 (1) ◽

pp. 15 ◽

Cited By ~ 1

Author(s):

Linde Peeters ◽

Siel Daelemans ◽

Yvan Vandenplas

Keyword(s):

Young Children ◽

Intestinal Microbiome ◽

Antibiotic Administration ◽

Gastrointestinal Microbiome ◽

Intestinal Dysbiosis ◽

Pros And Cons ◽

Inflammatory Bowel ◽

Antibiotic Associated Diarrhoea ◽

Infants And Young Children

The gastrointestinal microbiome is crucial for the development of a balanced immune system. Antibiotics are frequently administered to infants and cause intestinal dysbiosis. This narrative review highlights the long term health consequences of antibiotic administration to infants and young children. The necessity of administration of antibiotics should be well considered, since an association with short term consequences such as antibiotic associated diarrhoea and long term adverse effects such as overweight, inflammatory bowel syndrome, allergic disease have been reported. Conclusion: The pros and cons of antibiotic administration to infants and young children should be considered.

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Characterizing the Intestinal Microbiome in Infantile Colic

Biological Research For Nursing ◽

10.1177/1099800415620840 ◽

2015 ◽

Vol 18 (3) ◽

pp. 307-315 ◽

Cited By ~ 14

Author(s):

Nancy E. Dubois ◽

Katherine E. Gregory

Keyword(s):

Health Care ◽

Health Care Providers ◽

Intestinal Microbiome ◽

Infantile Colic ◽

Care Providers ◽

Microbial Composition ◽

Intestinal Dysbiosis ◽

Potential Association ◽

Microbiome Research ◽

The Impact

Approximately 20% of newborns will develop symptoms of infantile colic starting around 2 weeks of age. While health care providers have a greater understanding of the impact that inconsolable crying has on family dynamics, maternal–infant bonding, and health care resources, opportunities for study still exist in the area of intestinal microbiome research. Advances in molecular technologies utilizing 16S ribosomal RNA and ribosomal DNA created the opportunity for researchers to index the intestinal microbial composition to better understand its association with infantile colic. This integrative review provides a synopsis of the findings from five recent studies that utilized nonculture-based approaches to characterize the intestinal microbiome of infants with colic. Articles were identified through PubMed, CINAHL, and Google Scholar using the search terms colic, crying, fussiness, microbiome, and microbiota. The general aim of the research studies was to better understand the potential association of intestinal dysbiosis with the development of colic symptoms. The research found that infants who expressed symptoms of colic were colonized with significantly higher levels of Proteobacteria and exhibited lower bacterial diversity when compared to their unaffected counterparts. Additionally, colonization levels of Actinobacteria Bifidobacterium and Firmicute Lactobacilli were inversely related to the amount of crying and fussiness in newborns. The observed association of an imbalanced colonization of the intestines by noncommensal bacteria with the expression of infantile colic symptoms warrants further exploration.

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The Gut Microbiota-Derived Immune Response in Chronic Liver Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22158309 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8309

Author(s):

Sung-Min Won ◽

Eunju Park ◽

Jin-Ju Jung ◽

Raja Ganesan ◽

Haripriya Gupta ◽

...

Keyword(s):

Liver Disease ◽

Chronic Liver Disease ◽

Causative Factor ◽

Chronic Liver ◽

Intestinal Microbiome ◽

Future Research ◽

The Future ◽

Future Research Directions ◽

Excessive Intake ◽

And Function

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut–liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions.

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Adipose Tissue Inflammation Is Directly Linked to Obesity-Induced Insulin Resistance, while Gut Dysbiosis and Mitochondrial Dysfunction Are Not Required

Function ◽

10.1093/function/zqaa013 ◽

2020 ◽

Vol 1 (2) ◽

Cited By ~ 1

Author(s):

Heather L Petrick ◽

Kevin P Foley ◽

Soumaya Zlitni ◽

Henver S Brunetta ◽

Sabina Paglialunga ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Mitochondrial Dysfunction ◽

Intestinal Microbiome ◽

Mitochondrial Bioenergetics ◽

Obese Mice ◽

Gut Dysbiosis ◽

Intestinal Dysbiosis ◽

Adipose Inflammation

Abstract Obesity is associated with adipose tissue hypertrophy, systemic inflammation, mitochondrial dysfunction, and intestinal dysbiosis. Rodent models of high-fat diet (HFD)-feeding or genetic deletion of multifunctional proteins involved in immunity and metabolism are often used to probe the etiology of obesity; however, these models make it difficult to divorce the effects of obesity, diet composition, or immunity on endocrine regulation of blood glucose. We, therefore, investigated the importance of adipose inflammation, mitochondrial dysfunction, and gut dysbiosis for obesity-induced insulin resistance using a spontaneously obese mouse model. We examined metabolic changes in skeletal muscle, adipose tissue, liver, the intestinal microbiome, and whole-body glucose control in spontaneously hyperphagic C57Bl/6J mice compared to lean littermates. A separate subset of lean and obese mice was subject to 8 weeks of obesogenic HFD feeding, or to pair feeding of a standard rodent diet. Hyperphagia, obesity, adipose inflammation, and insulin resistance were present in obese mice despite consuming a standard rodent diet, and these effects were blunted with caloric restriction. However, hyperphagic obese mice had normal mitochondrial respiratory function in all tissues tested and no discernable intestinal dysbiosis relative to lean littermates. In contrast, feeding mice an obesogenic HFD altered the composition of the gut microbiome, impaired skeletal muscle mitochondrial bioenergetics, and promoted poor glucose control. These data show that adipose inflammation and redox stress occurred in all models of obesity, but gut dysbiosis and mitochondrial respiratory dysfunction are not always required for obesity-induced insulin resistance. Rather, changes in the intestinal microbiome and mitochondrial bioenergetics may reflect physiological consequences of HFD feeding.

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A Bronze-Tomato Enriched Diet Affects the Intestinal Microbiome under Homeostatic and Inflammatory Conditions

Nutrients ◽

10.3390/nu10121862 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1862 ◽

Cited By ~ 9

Author(s):

Marina Liso ◽

Stefania De Santis ◽

Aurelia Scarano ◽

Giulio Verna ◽

Manuela Dicarlo ◽

...

Keyword(s):

Intestinal Inflammation ◽

Bacterial Species ◽

Intestinal Bacteria ◽

Intestinal Microbiome ◽

Microbial Composition ◽

Inflammatory Conditions ◽

Intestinal Dysbiosis ◽

Bowel Diseases ◽

And Control ◽

Chronic Intestinal Inflammation

Inflammatory bowel diseases (IBD) are debilitating chronic inflammatory disorders that develop as a result of a defective immune response toward intestinal bacteria. Intestinal dysbiosis is associated with the onset of IBD and has been reported to persist even in patients in deep remission. We investigated the possibility of a dietary-induced switch to the gut microbiota composition using Winnie mice as a model of spontaneous ulcerative colitis and chow enriched with 1% Bronze tomato. We used the near isogenic tomato line strategy to investigate the effects of a diet enriched in polyphenols administered to mild but established chronic intestinal inflammation. The Bronze-enriched chow administered for two weeks was not able to produce any macroscopic effect on the IBD symptoms, although, at molecular level there was a significant induction of anti-inflammatory genes and intracellular staining of T cells revealed a mild decrease in IL17A and IFNγ production. Analysis of the microbial composition revealed that two weeks of Bronze enriched diet was sufficient to perturb the microbial composition of Winnie and control mice, suggesting that polyphenol-enriched diets may create unfavorable conditions for distinct bacterial species. In conclusion, dietary regimes enriched in polyphenols may efficiently support IBD remission affecting the intestinal dysbiosis.

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Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection

Chemotherapy ◽

10.1159/000515344 ◽

2021 ◽

Vol 66 (1-2) ◽

pp. 24-32

Author(s):

Ornella Spagnolello ◽

Claudia Pinacchio ◽

Letizia Santinelli ◽

Paolo Vassalini ◽

Giuseppe Pietro Innocenti ◽

...

Keyword(s):

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Intestinal Microbiome ◽

Current Evidence ◽

Evidence Based ◽

Intestinal Epithelial ◽

Limited Evidence ◽

Medical Treatments ◽

Intestinal Dysbiosis ◽

Evidence Based Therapy

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host’s microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response (“gut-lung axis”). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.

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Microbiome and Cardiovascular Disease in CKD

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.12691117 ◽

2018 ◽

Vol 13 (10) ◽

pp. 1598-1604 ◽

Cited By ~ 18

Author(s):

Anna Jovanovich ◽

Tamara Isakova ◽

Jason Stubbs

Keyword(s):

Cardiovascular Disease ◽

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Bacteria ◽

Local Environment ◽

Intestinal Microbiome ◽

Intestinal Barrier Function ◽

Barrier Dysfunction ◽

Negative Effects ◽

Intestinal Dysbiosis

Patients with CKD exhibit a disproportionate burden of cardiovascular mortality, which likely stems from the presence of unique, nontraditional risk factors that accompany deteriorating kidney function. Mounting evidence suggests that alterations to the intestinal microbiome in CKD may serve as one such risk factor. The human intestinal tract is home to >100 trillion micro-organisms made up of a collection of commensal, symbiotic, and pathogenic species. These species along with their local environment constitute the intestinal microbiome. Patients with CKD show intestinal dysbiosis, an alteration of the gut micro-organism composition and function. Recent evidence links byproducts of intestinal dysbiosis to vascular calcification, atherosclerosis formation, and adverse cardiovascular outcomes in CKD. CKD-associated intestinal dysbiosis may also be accompanied by defects in intestinal barrier function, which could further enhance the negative effects of pathogenic intestinal bacteria in the human host. Thus, intestinal dysbiosis, defective intestinal barrier function, and a reduced capacity for clearance by the kidney of absorbed bacterial byproducts may all potentiate the development of cardiovascular disease in CKD. This narrative review focuses on microbiome-mediated mechanisms associated with CKD that may promote atherosclerosis formation and cardiovascular disease. It includes (1) new data supporting the hypothesis that intestinal barrier dysfunction leads to bacterial translocation and endotoxemia that potentiate systemic inflammation, (2) information on the accumulation of dietary-derived bacterial byproducts that stimulate pathways promoting atheromatous changes in arteries and cardiovascular disease, and (3) potential interventions. Despite great scientific interest in and a rapidly growing body of literature on the relationship between the microbiome and cardiovascular disease in CKD, many important questions remain unanswered.

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