Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a severe respiratory illness and alters the gut microbiota, which dynamically interacts with the human immune system. Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens. Here, we describe critical factors affecting the microbiota in coronavirus disease 2019 (COVID-19) patients. These include, such as gut microbiota imbalance and gastrointestinal symptoms, the pattern of altered gut microbiota composition in COVID-19 patients, and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis. Moreover, we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration. The role of ACE2 in the digestive system, and control of its expression using the gut microbiota is discussed, highlighting the interactions between the lungs, the gut, and the brain during COVID-19 infection. Similarly, we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19. Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review. Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity. However, understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.     

Inflammation,microbiome and colorectal cancer disparity in African-Americans: Are there bugs in the genetics?

Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer (CRC). While environmental factors and socio-economic realities of race remain predominant contributors to CRC disparities in African-Americans (AAs), this review focuses on the biological mediators of CRC disparity, namely the under-appreciated influence of inherited ancestral genetic regulation on mucosal innate immunity and its interaction with the microbiome. There remains a poor understanding of mechanisms linking immune-related genetic polymorphisms and microbiome diversity that could influence chronic inflammation and exacerbate CRC disparities in AAs. A better understanding of the relationship between host genetics, bacteria, and CRC pathogenesis will improve the prediction of cancer risk across race/ethnicity groups overall.     

Gut microbiome: Linking together obesity,bariatric surgery and associated clinical outcomes under a single focus

Obesity is increasingly prevalent in the post-industrial era, with increased mortality rates. The gut microbiota has a central role in immunological, nutritional and metabolism mediated functions, and due to its multiplexity, it is considered an independent organ. Modern high-throughput sequencing techniques have allowed phylogenetic exploration and quantitative analyses of gut microbiome and improved our current understanding of the gut microbiota in health and disease. Its role in obesity and its changes following bariatric surgery have been highlighted in several studies. According to current literature, obesity is linked to a particular microbiota profile that grants the host an augmented potential for calorie release, while limited diversity of gut microbiome has also been observed. Moreover, bariatric surgery procedures represent effective interventions for sustained weight loss and restore a healthier microbiota, contributing to the observed fat mass reduction and lean mass increase. However, newer evidence has shown that gut microbiota is only partially recovered following bariatric surgery. Moreover, several targets including FGF15/19 (a gut-derived peptide), could be responsible for the favorable metabolic changes of bariatric surgery. More randomized controlled trials and larger prospective studies that include well-defined cohorts are required to better identify associations between gut microbiota, obesity, and bariatric surgery.     

Microbiome in the primary prevention of allergic diseases and bronchial asthma

Tremendous progress in the ability to identify and test the function of microorganisms in recent years has led to a much better understanding of the role of environmental and host microbiome in the development of immune function, allergic sensitization and asthma. In this review, the most recent findings on the relationships between environmental microbiota, respiratory, intestinal microbiome, the consequences of early-life microbial exposure type and gut–lung microbial axis and the development of asthma and atopy are summarized. The current perspective on gut and airway microbiome manipulation for the primary prevention of allergic diseases and asthma is also discussed.     

Nutrition,the gut microbiome and the metabolic syndrome

Metabolic syndrome is a lifestyle disease, determined by the interplay of genetic and environmental factors. Obesity is a significant risk factor for development of the metabolic syndrome, and the prevalence of obesity is increasing due to changes in lifestyle and diet. Recently, the gut microbiota has emerged as an important contributor to the development of obesity and metabolic disorders, through its interactions with environmental (e.g. diet) and genetic factors. Human and animal studies have shown that alterations in intestinal microbiota composition and shifts in the gut microbiome towards increased energy harvest are associated with an obese phenotype. However, the underlying mechanisms by which gut microbiota affects host metabolism still need to be defined.In this review we discuss the complexity surrounding the interactions between diet and the gut microbiota, and their connection to obesity. Furthermore, we review the literature on the effects of probiotics and prebiotics on the gut microbiota and host metabolism, focussing primarily on their anti-obesity potential.     

Gut microbiota in obesity

Obesity is a major global health problem determined by heredity and environment, and its incidence is increasing yearly. In recent years, increasing evidence linking obesity to the gut microbiota has been reported. Gut microbiota management has become a new method of obesity treatment. However, the complex interactions among genetics, environment, the gut microbiota, and obesity remain poorly understood. In this review, we summarize the characteristics of the gut microbiota in obesity, the mechanism of obesity induced by the gut microbiota, and the influence of genetic and environmental factors on the gut microbiota and obesity to provide support for understanding the complex relationship between obesity and microbiota. At the same time, the prospect of obesity research related to the gut microbiota is proposed.     

Colonic biogeography in health and ulcerative colitis

The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome.     

Gut Microbiota in Metabolic-associated Fatty Liver Disease and in Other Chronic Metabolic Diseases

The gut microbiome plays a key role in the health-disease balance in the human body. Although its composition is unique for each person and tends to remain stable throughout lifetime, it has been shown that certain bacterial patterns may be determining factors in the onset of certain chronic metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, metabolic-associated fatty liver disease (MAFLD), and metabolic syndrome. The gut-liver axis embodies the close relationship between the gut and the liver; disturbance of the normal gut microbiota, also known as dysbiosis, may lead to a cascade of mechanisms that modify the epithelial properties and facilitate bacterial translocation. Regulation of gut microbiota is fundamental to maintaining gut integrity, as well as the bile acids composition. In the present review, we summarize the current knowledge regarding the microbiota, bile acids composition and their association with MAFLD, obesity, T2DM and metabolic syndrome.     

The Role of Gut Microbiota and Genetic Susceptibility in the Pathogenesis of Pancreatitis

Pancreatitis is one of the most common inflammatory diseases of the pancreas caused by autodigestion induced by excessive premature protease activation. However, recognition of novel pathophysiological mechanisms remains a still challenge. Both genetic and environmental factors contribute to the pathogenesis of pancreatitis, and the gut microbiota is a potential source of an environmental effect. In recent years, several new frontiers in gut microbiota and genetic risk assessment research have emerged and improved the understanding of the disease. These investigations showed that the disease progression of pancreatitis could be regulated by the gut microbiome, either through a translocation influence or in a host immune response manner. Meanwhile, the onset of the disease is also associated with the heritage of a pathogenic mutation, and the disease progression could be modified by genetic risk factors. In this review, we focused on the recent advances in the role of gut microbiota in the pathogenesis of pancreatitis, and the genetic susceptibility in pancreatitis.     

Dietary pulses as a means to improve the gut microbiome,inflammation, and appetite control in obesity

A dysbiotic intestinal microbiome has been linked to chronic diseases such as obesity, which may suggest that interventions that target the microbiome may be useful in treating obesity and its complications. Appetite dysregulation and chronic systemic low-grade inflammation, such as that observed in obesity, are possibly linked with the intestinal microbiome and are potential therapeutic targets for the treatment of obesity via the microbiome. Dietary pulses (e.g., common beans) are composed of nutrients and compounds that possess the potential to modulate the gut microbiota composition and function which can in turn improve appetite regulation and chronic inflammation in obesity. This narrative review summarizes the current state of knowledge regarding the connection between the gut microbiome and obesity, appetite regulation, and systemic and adipose tissue inflammation. More specifically, it highlights the efficacy of interventions employing dietary common beans as a means to improve gut microbiota composition and/or function, appetite regulation, and inflammation in both rodent obesity and in humans. Collectively, results presented and discussed herein provide insight on the gaps in knowledge necessary for a comprehensive understanding of the potential of beans as a treatment for obesity while highlighting what further research is required to gain this understanding.     

Gut microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain–gut–microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.     

Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered

Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and ‘dysbiosis’ is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non‐IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High‐quality studies have shown that VSL#3 (a high‐potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.     

Alternations of gut microbiota composition in neonates conceived by assisted reproductive technology and its relation to infant growth

ABSTRACT

The gut microbiome in newborns may be strongly influenced by their intrinsic host microenvironmental factors (e.g., the gestational age) and has been linked to their short-term growth and potentially future health. It is yet unclear whether early microbiota composition is significantly different in newborns conceived by assisted reproductive technology (ART) when compared with those who were conceived spontaneously. Additionally, little is known about the effect of gut microbiota composition on weight gain in early infancy. We aimed to characterize the features and the determinants of the gut microbiome in ART newborns and to assess the impact of early microbiota composition on their weight gain in early infancy in mother-infant dyads enrolled in the China National Birth Cohort (CNBC). Among 118 neonates born by ART and 91 neonates born following spontaneous conception, we observed significantly reduced gut microbiota α-diversity and declined Bacteroidetes relative abundance in ART neonates. The microbiota composition of ART neonates was largely driven by specific ART treatments, hinting the importance of fetus intrinsic host microenvironment on the early microbial colonization. Following up these neonates for six months after their births, we observed the effects of gut microbiome composition on infant rapid weight gaining. Collectively, we identified features and determinants of the gut microbiota composition in ART neonates, and provided evidence for the importance of microbiota composition in neonatal growth.     

The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus

Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gut microbiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gut microbiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans.     

Microbiota of the gastrointestinal tract: Friend or foe?

The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection. The gut microbiota encodes over 3 million genes, which is approximately 150 times more than the total number of genes present in the human genome. Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites, changes in intestinal barrier function, and inflammation and can cause the development of a wide variety of diseases, such as diabetes, obesity, gastrointestinal disorders, cardiovascular issues, neurological disorders and oncological concerns. In this review, I consider issues related to the role of the microbiome in the regulation of intestinal barrier function, its influence on physiological and pathological processes occurring in the body, and potential new therapeutic strategies aimed at restoring the gut microbiome. Herewith, it is important to understand that the gut microbiota and human body should be considered as a single biological system, where change of one element will inevitably affect its other components. Thus, the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors, the role of which has not yet been fully elucidated.     

Factors that drive variation among gut microbial communities

Surveys of humans from around the world have revealed differences in gut microbiota composition among geographically separated populations. But because humans from the same regions often share common ancestry as well as dietary and cultural habits, most studies have not been able to differentiate among the effects of heritable factors and external factors on the composition of the gut microbiota. Here we discuss how the analysis of gut microbial communities of chimpanzees residing in Gombe Stream National Park has provided an unprecedented opportunity to measure the effects of external factors while controlling for heritable factors. The differences in gut microbiota composition between separated host populations of chimpanzees are due almost entirely to external factors, with the contribution of heritable factors to intraspecific variation in gut microbiota composition being too small to detect. The dominant influence of external factors in generating differences among the gut microbiota of our closest relatives lends promise to the possibility of manipulating the composition of the gut microbiome within human hosts. These results highlight the need for controlled studies that isolate the roles of specific external factors, such as diet, cultural practices and geography, in generating differences in the gut microbiota composition.     

Diet and Gut Microbial Function in Metabolic and Cardiovascular Disease Risk

Over the past decade, the gut microbiome has emerged as a novel and largely unexplored source of variability for metabolic and cardiovascular disease risk, including diabetes. Animal and human studies support several possible pathways through which the gut microbiome may impact health, including the production of health-related metabolites from dietary sources. Diet is considered important to shaping the gut microbiota; in addition, gut microbiota influence the metabolism of many dietary components. In the present paper, we address the distinction between compositional and functional analysis of the gut microbiota. We focus on literature that highlights the value of moving beyond surveys of microbial composition to measuring gut microbial functioning to delineate mechanisms related to the interplay between diet and gut microbiota in cardiometabolic health.     

The microbiome and obesity: Is obesity linked to our gut flora?

The human gut is a lush microbial ecosystem containing about 100 trillion microorganisms, whose collective genome, the microbiome, contains 100-fold more genes than the entire human genome. The symbiosis of our extended genome plays a role in host homeostasis and energy extraction from diet. In this article, we summarize some of the studies that have advanced the understanding of the microbiome and its effects on metabolism, obesity, and health. Metagenomic studies demonstrated that certain mixes of gut microbiota may protect or predispose the host to obesity. Furthermore, microbiota transplantation studies in germ-free murine models showed that the efficient energy extraction traits of obese-type gut flora are transmissible. The proposed methods by which the microbiome may contribute to obesity include increasing dietary energy harvest, promoting fat deposition, and triggering systemic inflammation. Future treatments for obesity may involve modulation of gut microbiota using probiotics or prebiotics.     

Gut microbiota and non-alcoholic fatty liver disease

BACKGROUND: Non-alcoholic fatty liver disease(NAFLD) is a common disorder with poorly understood pathogenesis. Beyond environmental and genetic factors,cumulative data support the causative role of gut microbiota in disease development and progression.DATA SOURCE: We performed a Pub Med literature search with the following key words: "non-alcoholic fatty liver disease","non-alcoholic steatohepatitis","fatty liver","gut microbiota" and "microbiome",to review the data implicating gut microbiota in NAFLD development and progression.RESULTS: Recent metagenomic studies revealed differences in the phylum and genus levels between patients with fatty liver and healthy controls. While bacteroidetes and firmicutes remain the dominant phyla among NAFLD patients,their proportional abundance and genera detection vary among different studies. New techniques indicate a correlation between the methanogenic archaeon(methanobrevibacter smithii) and obesity,while the bacterium akkermanshia municiphila protects against metabolic syndrome. Among NAFLD patients,small intestinal bacterial overgrowth detected by breath tests might induce gut microbiota and host interactions,facilitating disease development.CONCLUSIONS: There is evidence that gut microbiota participates in NAFLD development through,among others,obesity induction,endogenous ethanol production,inflammatory response triggering and alterations in choline metabolism. Further studies with emerging techniques are needed to further elucidate the microbiome and host crosstalk in NAFLD pathogenesis.