Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases

The composition of the mammalian gut microbiome is very important for the health and disease of the host. Significant correlations of particular gut microbiota with host immune responsiveness and various infectious and noninfectious host conditions, such as chronic enteric infections, type 2 diabetes, obesity, asthma, and neurological diseases, have been uncovered. Recently, research has moved on to exploring the causalities of such relationships. The metabolites of gut microbiota and those of the host are considered in a ‘holobiontic’ way. It turns out that the host’s diet is a major determinant of the composition of the gut microbiome and its metabolites. Animal models of bacterial and viral intestinal infections have been developed to explore the interrelationships of diet, gut microbiome, and health/disease phenotypes of the host. Dietary fibers can act as prebiotics, and certain bacterial species support the host’s wellbeing as probiotics. In cases of Clostridioides difficile-associated antibiotic-resistant chronic diarrhea, transplantation of fecal microbiomes has sometimes cured the disease. Future research will concentrate on the definition of microbial/host/diet interrelationships which will inform rationales for improving host conditions, in particular in relation to optimization of immune responses to childhood vaccines.     

Symbiotic gut microbes modulate human metabolic phenotypes

Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe–host interactions and the roles of individual bacterial species are obscure. We now demonstrate a“transgenomic” approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary samples from seven Chinese individuals (sampled twice) and to model the microbial–host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as “the characterization of key functional members of the microbiome that most influence host metabolism and hence health.” For example, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host–microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions.     

Exercise influence on the microbiome–gut–brain axis

ABSTRACT

The microbiome in the gut is a diverse environment, housing the majority of our bacterial microbes. This microecosystem has a symbiotic relationship with the surrounding multicellular organism, and a balance and diversity of specific phyla of bacteria support general health. When gut bacteria diversity diminishes, there are systemic consequences, such as gastrointestinal and psychological distress. This pathway of communication is known as the microbiome–gut–brain axis. Interventions such as probiotic supplementation that influence microbiome also improve both gut and brain disorders. Recent evidence suggests that aerobic exercise improves the diversity and abundance of genera from the Firmcutes phylum, which may be the link between the positive effects of exercise on the gut and brain. The purpose of this review is to explain the complex communication pathway of the microbiome–gut–brain axis and further examine the role of exercise on influencing this communication highway.     

Gut microbiome in multiple sclerosis: The players involved and the roles they play

The human gut contains trillions of bacteria (microbiome) that play a major role in maintaining a healthy state for the host. Perturbation of this healthy gut microbiome might be an important environmental factor in the pathogenesis of inflammatory autoimmune diseases such as multiple sclerosis (MS). Others and we have recently reported that MS patients have gut microbial dysbiosis (altered microbiota) with the depletion of some and enrichment of other bacteria. However, the significance of gut bacteria that show lower or higher abundance in MS is unclear. The majority of gut bacteria are associated with certain metabolic pathways, which in turn help in the maintenance of immune homeostasis of the host. Here we discuss recent MS microbiome studies and the possible mechanisms through which gut microbiome might contribute to the pathogenesis of MS.     

The gut microbial influence on cholestatic liver disease

Patients with cholestatic liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) have a different gut microbiome composition than healthy controls. In contrast with PBC, PSC has a strong association with inflammatory bowel disease and is the prototypical disease of the gut‐liver axis. Still, there are some distinct overlapping microbial features in the microbiome of patients with PSC and PBC suggesting similarities in cholestatic diseases, although the possible pathogenetic involvement of these shared microbial changes is unknown. Herein, we present an overview of the available data and discuss the relevance for potential disease relevant host‐microbiota interactions. In general, the microbiome interacts with the host via the immunobiome (interactions between the host immune system and the gut microbiome), the endobiome (where the gut microbiome contributes to host physiology by producing or metabolizing endogenous molecules) and the xenobiome (gut microbial transformation of exogenous compounds, including nutrients and drugs). Experimental and human observational evidence suggest that the presence and functions of gut microbes are relevant for the severity and progression of cholestatic liver disease. Interestingly, the majority of new drugs that are currently being tested in PBC and PSC in clinical trials act on bile acid homeostasis, where the endobiome is important. In the future, it will be paramount to perform longitudinal studies, through which we can identify new intervention targets, biomarkers or treatment‐stratifiers. In this way, gut microbiome‐based clinical care and therapy may become relevant in cholestatic liver disease within the foreseeable future.     

Consequences of bile salt biotransformations by intestinal bacteria

Emerging evidence strongly suggest that the human “microbiome” plays an important role in both health and disease. Bile acids function both as detergents molecules promoting nutrient absorption in the intestines and as hormones regulating nutrient metabolism. Bile acids regulate metabolism via activation of specific nuclear receptors (NR) and G-protein coupled receptors (GPCRs). The circulating bile acid pool composition consists of primary bile acids produced from cholesterol in the liver, and secondary bile acids formed by specific gut bacteria. The various biotransformation of bile acids carried out by gut bacteria appear to regulate the structure of the gut microbiome and host physiology. Increased levels of secondary bile acids are associated with specific diseases of the GI system. Elucidating methods to control the gut microbiome and bile acid pool composition in humans may lead to a reduction in some of the major diseases of the liver, gall bladder and colon.     

Life-long dynamics of the swine gut microbiome and their implications in probiotics development and food safety

ABSTRACT

The swine gut microbiome has received remarkable attention in recent years given that pigs serve not only as important sources for animal-derived food but also as excellent biomedical models for human health. However, despite recent advances in the understanding of the swine gut microbiome, many important biological and ecological questions are still largely unanswered. In a recent study, we characterized the life-long dynamics of the swine gut microbiome from birth to market. We showed distinct shifts in gut microbiome structure along different growth stages mainly driven by diet. Here, we summarize these discoveries and provide additional data related to the core swine gut microbiome, probiotics development in the swine industry, and foodborne pathogens in the pork supply chain.     

Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease

The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic "inputs." These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.     

The human gut microbiome: Implications for future health care

In their intestine, humans possess an “extended genome” of millions of microbial genes—the microbiome. Because this complex symbiosis influences host metabolism, physiology, and gene expression, it has been proposed that humans are complex biologic “superorganisms.” Advances in microbiologic analysis and systems biology are now beginning to implicate the gut microbiome in the etiology of localized intestinal diseases such as the irritable bowel syndrome, inflammatory bowel disease, and colon cancer. These approaches also suggest possible links between the gut and previously unassociated systemic conditions such as type 2 diabetes and obesity. The elucidation of the intestinal microbiome is therefore likely to underpin future disease prevention strategies, personalized health care regimens, and the development of novel therapeutic interventions. This review summarizes the research that is defining our understanding of the intestinal microbiome and highlights future areas of research in gastroenterology and human health in which the intestinal microbiome will play a significant role.     

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.     

New prebiotics by ketone donation

Integrity of the microbiome is an essential element for human gut health. 3-Hydroxybutyrate (3HB) secreted into the gut lumen has gained attention as a regulator of gut physiology, including stem cell expansion. In this opinion, I propose new prebiotics leading to gut health by use of a ketone (3HB) donor. When exogenous 3HB is supplied through ketone donation, it has the potential to markedly improve gut health by altering the gut microbiome and systemic metabolic status. Poly-hydroxybutyrate (PHB) donates 3HB and primarily influences microbiota, making it an effective prebiotic for improving the gut environment. Thus, exogenous 3HB donation to the lumen of the gut may aid gut health by maintaining the integrity of microbiome.     

Associations between the gut microbiome and metabolic,inflammatory, and appetitive effects of sleeve gastrectomy

The complex and multifactorial etiology of obesity creates challenges for its effective long-term management. Increasingly, the gut microbiome is reported to play a key role in the maintenance of host health and wellbeing, with its dysregulation associated with chronic diseases such as obesity. The gut microbiome is hypothesized to contribute to obesity development and pathogenesis via several pathways involving food digestion, energy harvest and storage, production of metabolites influencing satiety, maintenance of gut barrier integrity, and bile acid metabolism. Moreover, the gut microbiome likely contributes to the metabolic, inflammatory, and satiety benefits and sustained weight-loss effects following bariatric procedures such as sleeve gastrectomy. While the field of gut microbiome research in relation to obesity and sleeve gastrectomy outcomes is largely in its infancy, the gut microbiome nonetheless holds great potential for understanding some of the mechanisms behind sleeve gastrectomy outcomes as well as for optimizing post-surgery benefits. This review will explore the current literature within the field as well as discuss the current limitations, including the small sample size, variability in methodological approaches, and lack of associative data, which need to be addressed in future studies.     

Gut microbiome in allogeneic HCT survivors: The insults are gone but the damage lingers

The gut microbiome is an important regulator of health and disease. The report by Hino et al. suggests that damage to the microbiome, inflicted before and soon after allogeneic haematopoietic progenitor cell transplantation, does not heal by itself, most likely with consequences for late transplantation outcomes. Commentary on: Hino et al. Prolonged gut microbial alterations in post-transplant survivors of allogeneic haematopoietic stem cell transplantation. Br J Haematol 2023;200:725-737.     

The gut microbiome stability is altered by probiotic ingestion and improved by the continuous supplementation of galactooligosaccharide

ABSTRACT

The stable gut microbiome plays a key role in sustaining host health, while the instability of gut microbiome also has been found to be a risk factor of various metabolic diseases. At the ecological and evolutionary scales, the inevitable competition between the ingested probiotic and indigenous gut microbiome can lead to an increase in the instability. It remains largely unclear if and how exogenous prebiotic can improve the overall gut microbiome stability in probiotic consumption. In this study, we used Lactobacillus plantarum HNU082 (Lp082) as a model probiotic to examine the impact of the continuous or pulsed supplementation of galactooligosaccharide (GOS) on the gut microbiome stability in mice using shotgun metagenomic sequencing. Only continuous GOS supplement promoted the growth of probiotic and decreased its single-nucleotide polymorphisms (SNPs) mutation under competitive conditions. Besides, persistent GOS supplementation increased the overall stability, reshaped the probiotic competitive interactions with Bacteroides species in the indigenous microbiome, which was also evident by over-abundance of carbohydrate-active enzymes (CAZymes) accordingly. Also, we identified a total of 793 SNPs arisen in probiotic administration in the indigenous microbiome. Over 90% of them derived from Bacteroides species, which involved genes encoding transposase, CAZymes, and membrane proteins. However, neither GOS supplementation here de-escalated the overall adaptive mutations within the indigenous microbes during probiotic intake. Collectively, our study demonstrated the beneficial effect of continuous prebiotic supplementation on the ecological and genetic stability of gut microbiomes.     

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.     

Bacterial symbioses of the medicinal leech Hirudo verbana

Gastrointestinal microbiomes play important roles in the health and nutrition of animals and humans. The medicinal leech, Hirudo verbana, serves as a powerful model for the study of microbial symbioses of the gut, due to its naturally limited microbiome compared with other popular models, the ability to cultivate the most abundant microbes, and genetically manipulate one of them, Aeromonas veronii. This review covers the relevance and application of leeches in modern medicine as well as recent discoveries detailing the nature of the gut microbiome. Additionally, the dual life-style of A. veronii allows one to do direct comparisons between colonization factors for beneficial and pathogenic associations, and relevant findings are detailed with respect to their role within the host and pathogenicity to other animals.     

Skin exposure to sunlight: a factor modulating the human gut microbiome composition

ABSTRACT

Background: The gut microbiome has been increasingly acknowledged as playing a pivotal role in human health. Therefore, a number of studies have focused on variables that impact its microbial structure and consequent functionality. A wide range of factors, such as diet, age, sex, life stage, behavior, ethnicity, and diseases have been considered, and strong links were set out. However, some aspects regarding the microbiome determinants are still under-explored. Discussion: Recently, Bosman et al. presented evidence that skin exposure to narrowband UVB light modulated the gut microbiome of a specific human cohort. This cohort presented an increase of biodiversity, Firmicutes and Proteobacteria, and a decrease of Bacteroidetes. Based on these findings, we revisited our data on a hunter-gatherer gut microbiome (Yanomami) and identified similarities in the gut microbiome of these two cohorts. Both presented a high abundance of Proteobacteria, which had been observed as a unique feature in the Yanomami gut microbiome, and based on Bosman et al study, could be associated with their natural sunlight exposure. Conclusion: In this commentary, we would like to point out that the human lifestyle concerning sunlight exposure should be considered as one force modulating the gut microbiome, highlighting, as proposed by Bosman et al, a novel skin-gut axis which is associated with health and disease.     

Elucidating the role of the host genome in shaping microbiome composition

A major goal of microbiome research is to identify the factors that determine bacterial composition within and upon a host. Environmental factors are thought to play a large role, such as diet in determining gut microbiome composition and moisture in determining skin microbiome composition. The role of host genetics, however, has been a source of debate in the literature. Recently, we examined the association of host genetics with human gut microbiome composition in the Hutterites, a population that lives and eats communally. We identified heritable bacterial taxa and host genetic loci associated with their abundances. In this addendum, I put these results into a broader context along with other recent studies of microbiome heritability, and synthesize common themes that appear across organisms and tissues, such as the relatively small extent genetics plays compared to environment and the role of host genetic variation in immune response and barrier integrity.