Microbiome: Friend or Friendly Foe.

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

The agents we now know as bacteria have been known for centuries to play a key role in certain kinds of illnesses and ailments. But aside from infectious diseases, the communities of microbes we carry in specific parts of our bodies—our microbiomes—are a relatively new topic in human health. Now this field of study has taken an evolutionary leap forward with new research showing human microbiomes may play a far greater role in environ-mental health than ever imagined. The excitement around this field was obvious at a National Academy of Sciences (NAS) workshop on the interplay of the microbiomes, environ-mental agents, and human health held 27–28 April 2011,1 where talks by researchers working in this area inspired numerous “eureka!” moments. New findings about the ways in which human microbiomes transform arsenic and mercury—two of our most prevalent and well-defined external human health hazards—suggest the role of commensal bacteria may equal or exceed that of genetic polymorphisms that regulate metal transformations within the body, says Ellen Silbergeld, a professor of environmental health sciences at the Johns Hopkins University Bloomberg School of Public Health. The implications of these new insights are staggering. Environmental health scientists may need to expand the toxicokinetics of metals and other environmental agents, as well as associated biomarkers, to include the microbial component. “This is a huge thing that has never been thought of before in environmental health sciences,” Silbergeld told workshop attendees. Emerging findings also demand a re-examination of what it means to be exposed to environmental agents, Silbergeld says. To a toxicologist, she explains, a contaminant is only “in the body” once it has crossed from the external environment into circulating blood, or a cell, or an organ. But new findings suggest biologically relevant transformations may take place prior to absorption, when contaminants interact with the microbiome in the mouth, intestines, or other tissues. Because of the metabolic processes mediated by microbiomes, a great deal of what toxicologists attribute to human metabolism—such as methylation of arsenic—may actually take place at least in part before contaminants cross into the internal environment of our bodies.

Introduction The literature data indicate that bacterial vaginosis (BV) increases the risk of development of lower urinary tract infections (LUTI). Thus, it is reasonable to assume that the use of probiotics, in particular Lactoginal, can be effective in preventing relapses of LUTI. Aim To study the efficiency of probiotics, particularly Lactoginal, for the prevention of recurrent LUTI and BV. Materials and methods A total of 120 women with chronic recurrent bacterial cystitis in the acute stage and concomitant bacterial vaginosis were randomized into two groups of 60 patients. In group 1, standard antibacterial therapy was used according to guidelines of professional societies. In group 2, vaginal probiotic Lactoginal was prescribed after standard treatment. Results The results obtained in this study correspond to the literature data. The additional use of probiotics in the complex therapy of chronic lower urinary tract inflammation contributed to the normalization of the lactobacilli concentration in 93% of cases, in contrast to standard antibacterial therapy, after which the normal flora was preserved only in 40% of cases. In addition, a reduction in the number of relapses of BV was seen. Moreover, it was found that in the group of patients treated with Lactoginal, there was 18.3% less recurrence of cystitis within 6 months than in the control group (p Conclusion The use of probiotics, in particular, Lactoginal vaginal capsules, in women with BV after antibacterial therapy contributes to a faster recovery and longer preservation of the normal vaginal flora, which allows to the prolongate the relapse-free period of both chronic bacterial cystitis and BV.

Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease with a high prevalence in children and adults. The disease characterized by pruritus, recurrent course is associated with other allergic conditions such as food allergies and asthma, forming the concept of “atopic march”. Genetic mutations affect the barrier function of the skin, creating conditions for allergens to penetrate and inflammation to develop. Environmental factors, including air pollution, nutrition, and microbiota, also play a significant role in the etiology and pathogenesis of AD. Nutrition during infancy and childhood is a key factor influencing growth and development in childhood, contributing to health and disease prevention throughout life. Breastfeeding and the diversity of the mother’s diet may influence the risk of AD in children. The consumption of certain foods during pregnancy and the specifics of complementary feeding may contribute to the development or decrease the risk of allergy in the child. The gut microbiota plays an important role in modulating immune responses and tolerance to food allergens. Scopus, Web of Science, Medline, The Cochrane Library, EMBASE, Global Health and RISC databases were used to create this review article. The article analyzes the literature on the peculiarities of the preventive diet in pregnant women, nursing mothers, and children in families with an aggravated hereditary history of atopic dermatitis. The review emphasizes the need for further research to identify the influence of early life nutrition on the risk of allergic diseases. The article discusses current approaches to the prevention and treatment of AD, including the use of probiotics, dietary diversity, and breastfeeding support as meaningful strategies to reduce the risk of AD and allergic diseases in children.

Microbiomes are niche ecosystems found on and within eukaryotic hosts. Interactions between microbiomes and their multicellular hosts are numerous, many of them being mediated or influenced by volatile organic compounds (VOCs). The relationships between the human microbiome and host physiology, health and disease have been extensively studied, yet mechanistic and molecular understanding remains lacking. To date, only a few of microbial-derived molecules are characterized as mediators of microbe–host communications. While bacteria produce a variety of VOCs with chemical characteristics that allow unique communications with the host, the human gut microbiome VOC profile has not yet been fully explored. In this chapter, we summarize a few examples of molecules that have been studied as communication mediators between the microbiome and the host and that are recognized as VOCs. The goal is to stress the importance of microbial VOC-specific research as a new and unexplored field of research with high potential.

Probiotics are live nonpathogenic microorganisms. Many of these microorganisms are part of the normal human gut flora, where they live in a symbiotic relationship. Probiotics have been used to treat gastrointestinal (GI) and non-GI medical conditions. However, the data supporting their use are often conflicting, especially for non-GI-associated illnesses. The strongest evidence supporting the use of probiotics is related to the treatment of acute diarrhea and pouchitis. Atopic eczema in children and genitourinary infections are the only non-GI-related medical conditions where probiotics may have some beneficial effects. Product selection and dosing are not the same in all conditions, and the beneficial effects of each probiotic strain cannot be generalized.The purpose of this article is to provide most recent information about probiotics and its uses. In contrast with previously published reviews on probiotics, we also discuss the composition of various products (Table 1), indications for their use (Table 2), product selection, and dosing of probiotics.Probiotics are safe and appear to exert some beneficial effects in GI-related illnesses. The use of probiotics in non-GI illnesses is not sufficiently supported by current data.

Lateral gene transfer (LGT), also known as horizontal gene transfer, facilitates genomic diversification in microbial populations. While previous work has surveyed LGT in human-associated microbial isolate genomes, the landscape of LGT arising in personal microbiomes is not well understood, as there are no widely adopted methods to characterize LGT from complex communities. Here we developed, benchmarked and validated a computational algorithm (WAAFLE or Workflow to Annotate Assemblies and Find LGT Events) to profile LGT from assembled metagenomes. WAAFLE prioritizes specificity while maintaining high sensitivity for intergenus LGT. Applying WAAFLE to >2,000 human metagenomes from diverse body sites, we identified >100,000 high-confidence previously uncharacterized LGT (~2 per microbial genome-equivalent). These were enriched for mobile elements, as well as restriction-modification functions associated with the destruction of foreign DNA. LGT frequency was influenced by biogeography, phylogenetic similarity of involved pairs (for example, Fusobacterium periodonticum and F. nucleatum) and donor abundance. These forces manifest as networks in which hub taxa donate unequally with phylogenetic neighbours. Our findings suggest that human microbiome LGT may be more ubiquitous than previously described.

Bile acid metabolism by the gut microbiome exerts both beneficial and harmful effects on host health. Microbial bile salt hydrolases (BSHs), which initiate bile acid metabolism, exhibit both positive and negative effects on host physiology. In this study, 5,790 BSH homologs were collected and classified into seven clusters based on a sequence similarity network. Next, the abundance and distribution of BSH in 380 metagenomes from healthy participants were analyzed. It was observed that different clusters occupied diverse ecological niches in the human microbiome and that the clusters with signal peptides were relatively abundant in the gut. Then, the association between BSH clusters and 12 human diseases was analyzed by comparing the abundances of BSH genes in patients (n = 1,605) and healthy controls (n = 1,540). The analysis identified a significant association between BSH gene abundance and 10 human diseases, including gastrointestinal diseases, obesity, type 2 diabetes, liver diseases, cardiovascular diseases, and neurological diseases. The associations were further validated by separate cohorts with inflammatory bowel diseases and colorectal cancer. These large-scale studies of enzyme sequences combined with metagenomic data provide a reproducible assessment of the association between gut BSHs and human diseases. This information can contribute to future diagnostic and therapeutic applications of BSH-active bacteria for improving human health.

ABSTRACTMetagenome analyses of the human microbiome suggest that horizontal gene transfer (HGT) is frequent in these rich and complex microbial communities. However, so far, only a few HGT studies have been conducted in vivo. In this work, three different systems mimicking the physiological conditions encountered in the human digestive tract were tested, including (i) the TNO gastro-Intestinal tract Model 1 (TIM-1) system (for the upper part of the intestine), (ii) the ARtificial COLon (ARCOL) system (to mimic the colon), and (iii) a mouse model. To increase the likelihood of transfer by conjugation of the integrative and conjugative element studied in the artificial digestive systems, bacteria were entrapped in alginate, agar, and chitosan beads before being placed in the different gut compartments. The number of transconjugants detected decreased, while the complexity of the ecosystem increased (many clones in TIM-1 but only one clone in ARCOL). No clone was obtained in a natural digestive environment (germfree mouse model). In the human gut, the richness and diversity of the bacterial community would offer more opportunities for HGT events to occur. In addition, several factors (SOS-inducing agents, microbiota-derived factors) that potentially increase in vivo HGT efficiency were not tested here. Even if HGT events are rare, expansion of the transconjugant clones can happen if ecological success is fostered by selecting conditions or by events that destabilize the microbial community.IMPORTANCE The human gut microbiota plays a key role in maintaining normal host physiology and health, but its homeostasis is fragile. During their transit in the gastrointestinal tract, bacteria conveyed by food can exchange genes with resident bacteria. New traits acquired by HGT (e.g., new catabolic properties, bacteriocins, antibiotic resistance) can impact the gut microbial composition and metabolic potential. We showed here that TIM-1, a system mimicking the upper digestive tract, is a useful tool to evaluate HGT events in conditions closer to the physiological ones. Another important fact pointed out in this work is that Enterococcus faecalis is a good candidate for foreign gene acquisition. Due to its high ability to colonize the gut and acquire mobile genetic elements, this commensal bacterium could serve as an intermediate for HGT in the human gut.

Human intestinal microbiota comprises bacteria, viruses, fungi, yeasts and bacteriophages. The human microbiota has a fundamental role in host physiology and pathology. This community starts to develop at birth and continues for two to three years, until it reaches a stable composition. It, however, continues to be influenced by different environmental and lifestyle factors throughout the host’s lifespan. It has now become apparent that human gut microbiota plays a fundamental role in human health and physiology. Increasing evidence in last ten years has shown that intestinal bacteria can affect the central nervous system and behavior. The nervous system and the gastrointestinal tract are connected through a bidirectional network of signaling pathways called the gut–brain axis, which consists of multiple mechanisms including the vagus nerve, the immune system and bacterial metabolites and products. Diet is one of the major factors involved in shaping the composition of human gut microbiota. One of the emerging areas of research is whether and how diet can affect the nervous system via its effect on gut microbiota. The majority of studies have employed animal models to advance our understanding of the role of nutritional interventions on the microbiota–gut–brain axis and its potential benefits for mental health. Although animal studies have shown great promise, evidence from human clinical studies is still limited.

Bile is a biological fluid synthesized in the liver, mainly constituted by bile acids and cholesterol, which functions as a biological detergent that emulsifies and solubilizes lipids, thereby playing an essential role in fat digestion. Besides, bile acids are important signaling molecules that regulate key functions at intestinal and systemic levels in the human body, affecting glucose and lipid metabolism, and immune homeostasis. Apart from this, due to their amphipathic nature, bile acids are toxic for bacterial cells and, thus, exert a strong selective pressure on the microbial populations inhabiting the human gut, decisively shaping the microbial profiles of our gut microbiota, which has been recognized as a metabolic organ playing a pivotal role in host health. Remarkably, bacteria in our gut also display a range of enzymatic activities capable of acting on bile acids and, to a lesser extent, cholesterol. These activities can have a direct impact on host physiology as they influence the composition of the intestinal and circulating bile acid pool in the host, affecting bile homeostasis. Given that bile acids are important signaling molecules in the human body, changes in the microbiota-residing bile biotransformation ability can significantly impact host physiology and health status. Elucidating ways to fine-tune microbiota-bile acids-host interplay are promising strategies to act on bile and cholesterol-related disorders. This manuscript summarizes the current knowledge on bile and cholesterol metabolism by intestinal bacteria, as well as its influence on host physiology, identifying knowledge gaps and opportunities to guide further advances in the field.

Should the Human Microbiome Be Considered When Developing Vaccines?

The interaction and co-evolution between the gut microbiome and the host play important roles in the host's physiology, nutrition, and health. Diet is considered an important driver of differences in the gut microbiota; however, research on the relationship between the gut microbiota and diet in Asian elephants remains limited. In this study, we explored the gut microbiota structure and its relationship with diet in different populations of Asian elephants through metagenomic sequencing, combined with previously published dietary data. This study found that the dominant gut microbiota of Asian elephants includes the phyla Bacillota (29.85% in BP, 22.79% in RC, 21.89% in SM, 31.67% in ML, and 33.00% in NGH), Bacteroidota (25.25% in BP, 31.44% in RC, 16.44% in SM, 25.73% in ML, and 23.74% in NGH), and Spirochaetota (3.49% in BP, 6.18% in RC, 1.71% in SM, 2.69% in ML, and 3.52% in NGH), with significant differences in the gut microbiota among different populations. Correlation analysis between the gut microbiota and diet revealed that dietary diversity did not directly affect the alpha diversity of the gut microbiota. However, specific food types might play a key role in shaping the gut microbiota structure by regulating the abundance of certain microbiota. This study reveals significant differences in the gut microbiota structure among different populations of Asian elephants and explores the impact of diet on the structure. The results provide foundational data for a deeper understanding of the gut microbiota structure of Asian elephants and offer important references for the scientific conservation and precise management strategies of this species.

World Gastroenterology Organisation practice guideline: Probiotics and prebiotics

Bacteriophages (phages) dramatically shape microbial community composition, redistribute nutrients via host lysis and drive evolution through horizontal gene transfer. Despite their importance, much remains to be learned about phages in the human microbiome. We investigated the gut microbiomes of humans from Bangladesh and Tanzania, two African baboon social groups and Danish pigs; many of these microbiomes contain phages belonging to a clade with genomes >540 kilobases in length, the largest yet reported in the human microbiome and close to the maximum size ever reported for phages. We refer to these as Lak phages. CRISPR spacer targeting indicates that Lak phages infect bacteria of the genus Prevotella. We manually curated to completion 15 distinct Lak phage genomes recovered from metagenomes. The genomes display several interesting features, including use of an alternative genetic code, large intergenic regions that are highly expressed and up to 35 putative transfer RNAs, some of which contain enigmatic introns. Different individuals have distinct phage genotypes, and shifts in variant frequencies over consecutive sampling days reflect changes in the relative abundance of phage subpopulations. Recent homologous recombination has resulted in extensive genome admixture of nine baboon Lak phage populations. We infer that Lak phages are widespread in gut communities that contain the Prevotella species, and conclude that megaphages, with fascinating and underexplored biology, may be common but largely overlooked components of human and animal gut microbiomes.