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Review

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

by
Ulrich Desselberger
Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
Viruses 2021, 13(8), 1601; https://doi.org/10.3390/v13081601
Submission received: 1 June 2021 / Revised: 29 July 2021 / Accepted: 9 August 2021 / Published: 12 August 2021
(This article belongs to the Special Issue Pathogenesis and Immunity of Enteric Virus Infections)
Review Reports Versions Notes

Abstract

:
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.

1. Introduction

The human gut microbiota, comprising bacteria, viruses, fungi, protozoa, and parasites and comprehensively termed the gut microbiome, have received increased attention for about a decade, when it was recognized that their commensal or symbiotic relationship is of great importance for human health, including immune responses correlated with protection from infection or disease [1,2,3,4]. Most of the microbiome data relate to the bacteria (bacteriome) and viruses (virome) populating the gut. Observational studies initially reported on cotemporal correlations of the composition of the gut microbiome with immune responses or disease outcome [5,6]. More recent studies aimed at identifying causal relationships between metabolic products of the gut microbiome and the host in health and disease [7,8,9]. This review emphasizes the importance of the transition from observational correlation studies to studies exploring causal microbiome–host relationships, which will provide data for rational developments of microbiota as probiotic agents.

2. The Intestinal Microbiome

The main bacterial phyla present in the gut are Proteobacteria, Bacteriodetes, Firmicutes, and Actinobacteria, with their total number estimated to be 1014 particles, and populating mainly the colon [10,11]. The gut microbiota in infants are originally similar to those of the mother but will develop by colonization with Bifidobacterium, Bacteroides, and Clostridium spp. [12], and the composition of the gut microbiome will highly depend on nutritional/feeding and environmental conditions [4,13]. Viruses found in the gut are mainly members of the Picornaviridae, Reoviridae, Caliciviridae, and Astroviridae families, and of various families of bacteriophages; in addition, members of the Adenoviridae, Picobirnaviridae, Herpesviridae, and Retroviridae families can be present [14]. Many bacteria replicating in the gut are commensals or symbionts; some bacteria, viruses, and most protozoa and parasites are pathogenic. The microbial homeostasis in healthy individuals can be disturbed to become a ‘dysbiosis’, which may be associated with the development of disease [15]. It has been extensively documented that the gut microbiota of children growing up in low- or middle-income countries differ drastically from those of children in high-income countries [6,10,13]. The composition of the gut microbiome is of great importance for the development of a functional immune system, which defends against pathogenic microbes [16].
Viruses and bacteria interact in the gut in a complex way. Thus, bacteria exhibiting cell receptor-like molecules on their surface can interact with viruses, and the complexes may either be washed out of the gut or be taken up by gut epithelia [17,18]. Accordingly, treatment of mice with antibiotics (ABs) reduced the diarrhea caused by murine rotaviruses and enhanced rotavirus-specific IgA responses [19] or reduced the uptake of poliovirus/reovirus–Bacillus cereus complexes [20]. Norovirus infectivity was also reduced in AB-treated mice [21,22]. Mouse microbiota can be reconstituted after AB treatment or in germ-free (GF) animals: while the AB option is inexpensive, it may not eliminate all residual bacteria and also affect epithelial cells; the GF option is more cumbersome and may be affected by developmental defects [23]. In human adults, AB-mediated microbiome changes were shown to increase the replication of rotavirus vaccine [24]. Thus, enteric viral infections can be facilitated or inhibited by bacteria, and in turn, latently virus-infected animals can become resistant to particular bacterial infections [25,26]. Particular immunodeficient mouse strains were found to be resistant to rotavirus infection and disease. By treating the microbiota of these mice with heat, filtration, and ABs, it was discovered that the resistance was due to the presence of segmented filamentous bacteria (members of Clostridiales) growing in the terminal ileum, which seemed to directly neutralize the virus, possibly by interfering with its binding to host cell receptors. This represents a novel way of protecting mammals against rotavirus disease [27]; the cytokines IL-22 and IL-18 were also found to be involved in this protection [28]. In RV-infected neonatal mice, a loss of Lactobacillus spp. was detected in the ileum on day 1 p.i., accompanied by an increase in Bacteroides and Akkermania spp., which both digest mucin glycan. Simultaneously, a loss of mucin-producing goblet cells was observed, which had recovered on day 3 p.i. [29]. These data indicate that resident bacteria in the ileum participate in the promotion of RV infection. Mixed infections of children with RV and enteropathogenic E. coli resulted in an increase in the disease severity score compared to infection with RV alone [30].

3. Intestinal Microbiome and Immune Responses

3.1. In Humans

From observational studies, it has been recognized that the immune responses of children to oral or parenteral vaccines in low-income countries are often weak and that this finding correlated with the particular composition of the gut bacteriome of these children [31]. The presence of Clostridia and Proteobacteria correlated with a favorable immune response to rotavirus vaccination in Pakistan [32]. In Ghana, enrichment of Bifidobacteria was associated with a favorable immune response of children and that of Enterobacteria and Pseudomonas with low immune responses and lower protection [33]. The composition of the microbiome of high responders was similar to that of high responders in high-income countries [32,33]. No such differences were found in children receiving rotavirus vaccination in Nicaragua [34]. However, most evidence indicates that the composition of the intestinal microbiome is important for the improvement of vaccine efficacies [24,35]. The reasons for decreases in immune responses are complex. Besides the composition of the gut microbiome, malnutrition (including zinc deficiency and vitamin A and D avitaminoses), intestinal and extraintestinal coinfections, immunological immaturity (often linked with premature birth), the presence of maternal antibodies (transmitted via placenta), and host genetic factors play a role [3,36,37].

3.2. In Animals

The influence of the gut microbiome on enteric infections has been extensively studied in animal models. Thus, gnotobiotic (gn) piglets transplanted with ‘healthy’ human gut microbiota from children (HHGM: Proteobacteria, Bacteriodetes) or with microbiota from children with weak (‘unhealthy’) immune responses (UHGM: Proteobacteria and Firmicutes) differed in their reaction to challenge with human rotavirus: the HHGM-transplanted animals expanded Bacteriodetes and had less severe diarrhea and virus shedding than UHGM-transplanted animals, which maintained the high prevalence of Firmicutes spp. [38]. Similarly, neonatally GF piglets transplanted with a human infant’s fecal microbiome (HIFM) upon challenge had less severe rotavirus disease than nontransplanted piglets; a protein-deficient diet increased the severity of RV disease also in the HIFM-transplanted piglets [39].
In both human and animal vaccine studies, it has been shown that the composition of the gut microbiome is highly important for the efficacy of vaccines, e.g., against RV, poliovirus, and bacteria, such as Salmonella and Shigella [6,40].

4. Intestinal Microbiome–Host Interaction via Metabolites

In animal studies, it has become apparent that differences in the metabolism of bacteria may be important for the host’s health. Bacterial metabolites produced in the gut may enter the host via hematogenic spread and either be toxic or support the health of the gut or extraintestinal tissues. Metabolites of both microbes and host form a complex system, and humans have been termed as ‘holobionts’ in this concept [9]. Experiments aiming at discovering causal microbiome–host relationships were initiated [7]. Numerous microbial metabolites were shown to affect the host’s metabolic pathways and to be positively or negatively associated with metabolic diseases such as type 2 diabetes (T2D) or obesity [7]. For the microbiome–host relationship, the supply of polymeric compounds for bacterial fermentation in particular diets plays a very important role [8]. Some products of bacterial fermentation and selected bacterial species producing them are listed in Table 1. Of those metabolites:
  • Short-chain fatty acids (SCFAs) have anti-inflammatory activity [41] and can act as adjuvants to vaccines [42]; butyrate-producing bacteria were found to be beneficial as probiotics (see below) in children with idiopathic nephrotic syndrome by boosting the synthesis of Treg cells [43];
  • Products of tryptophan metabolism (kynurenine, indoles, and tryptamine) may be involved in neurological disease [44,45] or protect from colitis [44,46,47];
  • Spore-forming gut bacteria can modulate the production of serotonin (5-hydroxytryptamine) in entero-chromaffine cells and thus affect gut motility, platelet, and CNS functions [48];
  • Products of histidine fermentation may cause immune pathologies and be involved in asthma pathogenesis [49,50];
  • Imidazole propionate production is correlated with an increased risk for the development of T2D [51,52];
  • Dopamine is generated by bacterial decarboxylases from levodopa, used for the treatment of Parkinson’s disease [53,54];
  • P-cresol, a product of tyrosine fermentation, can reduce allergic airways inflammation [55];
  • Dietary and bacterially produced polyphenols have anti-inflammatory effects [56];
  • Host bile acids are deconjugated and transformed into secondary bile acids in the colon, where they can inhibit the growth of Clostridioides difficile [57], but are also associated with an increased risk of obesity development [58];
  • Trimethylamine-N-oxide, derived from bacterial metabolization of choline and carnitine, has been found to be associated with a risk to develop atherosclerosis and T2D [59,60,61];
  • Sphingolipids derived from Bacteroides spp. metabolism are important for intestinal bacterial homeostasis [62,63].
The interplay between diet, gut microbiota fermentation, and host cellular pathways leads to a complex microbe–host-produced spectrum of metabolites, strongly suggesting that the gut microbiome affects the host’s health in a much more general way than just by its influence on immune responses.

5. Intestinal Microbiome and Diet

In studying causal relationships between the gut microbiome composition and the mammalian host’s health phenotype, the transplantation of human gut microbiome to experimental animals has encountered the problem that not all human bacteria may survive in the new host, also due to the fact that animal and human diets differ substantially. This has been clearly demonstrated in a study by Rodriguez et al. [67], who showed that the basal diet of mice determined the long term composition of their gut microbiome and the mouse phenotypes to a greater extent than the transfer of largely different fecal microbiomes obtained from lean or obese human donors.
In order to overcome some of these problems, a mouse model for the study of diet–microbe–host interactions has been developed using the following procedure [68]:
  • A human simplified intestinal microbiota (SIM) consisting of 10 human bacterial strains able to metabolize dietary fibers was constructed;
  • SIM bacteria were transferred to GF mice;
  • Mice were kept on three different diets: chow (fiber-rich), high fat–high sucrose (low in fiber), and zero fat–high sucrose (low in fiber).
The system was used to study how the different diets may affect the abundance and the transcriptome of SIM bacteria, how SIM–diet interactions may affect the circulation of metabolites, and how this may affect the metabolism of the host. Preliminary results showed that:
  • The diet affected the SIM bacteria colonization and their fermentation capacity;
  • Diet–SIM bacteria interaction affected the systemic entry of SIM metabolites into the plasma of the host;
  • The host metabolism in turn depended on the diet taken.
A microbiota-directed complementary food prototype was developed for 12–18 m old malnourished children and been found to be beneficial for weight and height gain, increase in plasma protein levels, and population by Faecalibacterium and Bifidobacterium spp. [69].

6. Intestinal Microbiome and Infectious and Non-Infectious Diseases

Dysbiotic microbiomes can lead to intestinal infectious diseases such as inflammatory bowel disease, necrotizing enterocolitis, irritable bowel syndrome, chronic Clostridioides difficile diarrhea, and extraintestinal infectious diseases [70]. Microbiota research should focus on discovering causal links between human microbiota and infectious and immune-mediated diseases [71].
A combination of dietary conditions and altered gut microbiomes was found to be associated with T2D [52,67,72], obesity [73], nonalcoholic fatty liver disease [74,75], idiopathic nephrotic syndrome [43], and cardiovascular diseases such as hypertension [76] or atherosclerotic disease [60,61,77]. In detail, the pathogenic mechanisms are complex and often systemic. The metabolic potential of gut microbiota (see above) may generate bioactive compounds, which can interact with the host in various ways [61].

7. Diet, Prebiotics, and Intestinal Microbes as Probiotics

Prebiotics are components of food which support the growth of gut microorganisms beneficial for human health. They mainly consist of fibers, which nondigestible in the mammalian small intestine but suitable as substrates for bacteria in the colon, mainly Bifidobacteria and Lactobacillus. A major metabolic product of bacterial fermentation of starches is SCFAs, which have antibacterial activity [64,65]. Dietary polyphenols have been shown to have anti-inflammatory and possibly prebiotic activities [56]. Gnotobiotic mice colonized by a consortium of human gut-derived bacteria were fed different food-derived fibers; by administering retrievable artificial food particles, it was possible to identify bacterial species specialized in the degradation of particular types of fiber [78]. Analysis of the microbiota of a healthy Bangladeshi birth cohort enabled the identification of several covarying bacteria—potentially leading the way toward gut microbiota repair in undernourished children [79].
Different bacteria (Lactobacillus and Bifidobacterium spp.) living in mammalian guts as commensals have been proven to act as probiotics by improving immune responses to rotavirus vaccines in gn piglets [39,80,81,82,83,84,85,86]. Probiotic bacteria have also ameliorated health in weaned piglets challenged with Salmonella typhimurium [87] and in children with Salmonella and rotavirus gastroenteritis [88,89,90]. Lactobacillus reuteri was shown to decrease the pathogenicity of Clostridioides difficile by the generation of reactive oxygen species [91].
Symbiotics are defined as a mixture of beneficial bacteria (probiotics) and fibers (prebiotics) on which the bacteria feed. They can be used as food supplements, typically consisting of lactic acid bacteria (Lactobacillus paracasei, L. plantarum) and plant fibers (pectin from citrus fruits, inulin from chicory root, starch from corn) and are applied as a remedy for microbe-associated acute infantile and noninfectious chronic diarrheas [92].

8. Intestinal Microbes as Therapeutics

Fecal microbiota transplantation (FMT) is an established procedure to treat chronic, AB-resistant, Clostridioides difficile-associated chronic diarrhea [93,94]. However, the overall rate of clinical cure is variable, and major adverse clinical events are not rare [7,95]. Careful risk assessment is indicated [96].

9. Outlook and Future Research

Knowledge of the gut microbiome, including its establishment, evolution, changes, and association with intestinal and extraintestinal diseases has enormously increased during the past 10 years. In particular, the relationship between particular gut microbiome compositions and immune responsiveness to invading microbes or vaccines has been analyzed. However, increasingly, observational studies aiming at cotemporal correlations of microbiome composition and clinical symptoms have given way to investigations in which causal relationships between gut microbiome composition, diet, complex metabolic end products (of both the microbiome and the mammalian host), and clinical phenotypes are being explored. Such data will form a rational basis for the use of gut microbiomes as therapeutic or probiotic agents.
A list of topics that remain open for future research has been collated in Table 2. The molecular biology of the interaction of gut microbiome and host, the dependence of microbiota on diet, and the influence of the joint microbiome–host metabolome on health and disease require more detailed understanding and study. Factors determining eubiosis/dysbiosis in the microbiome–host relationship have to be identified in relation to host clinical phenotypes, particularly in children from low-income countries. Mechanisms determining the influence of probiotic bacterial metabolites on the host’s immune responses have to be defined. The use of probiotic bacteria for the improvement of extended programs of immunization (EPI) in low- and middle-income countries has to be explored and optimized.

Funding

This review received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The author declares no conflict of interest.

References

  1. Desselberger, U. The mammalian intestinal microbiome: Composition, interaction with the immune system, significance for vaccine efficacy, and potential for disease therapy. Pathogens 2018, 7, 57. [Google Scholar] [CrossRef] [Green Version]
  2. Quigley, E.M.M. Gut bacteria in health and disease. Gastroenterol. Hepatol. 2013, 9, 560–569. [Google Scholar]
  3. Vlasova, A.N.; Takanashi, S.; Miyazaki, A.; Rajashekara, G.; Saif, L.J. How the gut microbiome regulates host immune responses to viral vaccines. Curr. Opin. Virol. 2019, 37, 16–25. [Google Scholar] [CrossRef] [PubMed]
  4. Yatsunenko, T.; Rey, F.E.; Manary, M.J.; Trehan, I.; Dominguez-Bello, M.G.; Contreras, M.; Magris, M.; Hidalgo, G.; Baldassano, R.N.; Anokhin, A.P.; et al. Human gut microbiome viewed across age and geography. Nature 2012, 486, 222–227. [Google Scholar] [CrossRef] [PubMed]
  5. Chung, H.; Pamp, S.J.; Hill, J.A.; Surana, N.K.; Edelman, S.M.; Troy, E.B.; Reading, N.C.; Villablanca, E.J.; Wang, S.; Mora, J.R.; et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell 2012, 149, 1578–1593. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Huda, M.N.; Lewis, Z.; Kalanetra, K.M.; Rashid, M.; Ahmad, S.M.; Raqib, R.; Qadri, F.; Underwood, M.A.; Mills, D.A.; Stephensen, C.B. Stool microbiota and vaccine responses of infants. Pediatrics 2014, 134, e362–e372. [Google Scholar] [CrossRef] [Green Version]
  7. Koh, A.; Bäckhed, F. From association to causality: The role of the gut microbiota and its functional products on host metabolism. Mol. Cell 2020, 78, 584–596. [Google Scholar] [CrossRef]
  8. Krautkramer, K.A.; Fan, J.; Bäckhed, F. Gut microbial metabolites as multi-kingdom intermediates. Nat. Rev. Microbiol. 2021, 19, 77–94. [Google Scholar] [CrossRef]
  9. van de Guchte, M.; Blottière, H.M.; Doré, J. Humans as holobionts: Implications for prevention and therapy. Microbiome 2018, 6, 81. [Google Scholar] [CrossRef]
  10. Davenport, E.R.; Sanders, J.G.; Song, S.J.; Amato, K.R.; Clark, A.G.; Knight, R. The human microbiome in evolution. BMC Biol. 2017, 15, 127. [Google Scholar] [CrossRef]
  11. Thursby, E.; Juge, N. Introduction to the human gut microbiota. Biochem. J. 2017, 474, 1823–1836. [Google Scholar] [CrossRef] [PubMed]
  12. Arrieta, M.C.; Stiemsma, L.T.; Amenyogbe, N.; Brown, E.M.; Finlay, B. The intestinal microbiome in early life: Health and disease. Front Immunol. 2014, 5, 427. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Lin, A.; Bik, E.M.; Costello, E.K.; Dethlefsen, L.; Haque, R.; Relman, D.A.; Singh, U. Distinct distal gut microbiome diversity and composition in healthy children from Bangladesh and the United States. PLoS ONE 2013, 8, e53838. [Google Scholar] [CrossRef] [Green Version]
  14. Desselberger, U. Viral gastroenteritis. Medicine 2017, 45, 690–694. [Google Scholar] [CrossRef]
  15. Martinez, K.B.; Leone, V.; Chang, E.B. Microbial metabolites in health and disease: Navigating the unknown in search of function. J. Biol. Chem. 2017, 292, 8553–8559. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Martin, R.; Nauta, A.J.; Ben Amor, K.; Knippels, L.M.; Knol, J.; Garssen, J. Early life: Gut microbiota and immune development in infancy. Benef. Microbes 2010, 1, 367–382. [Google Scholar] [CrossRef]
  17. Karst, S.M. Viral safeguard: The enteric virome protects against gut inflammation. Immunity 2016, 44, 715–718. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. Monedero, V.; Buesa, J.; Rodríguez-Díaz, J. The interactions between host glycobiology, bacterial microbiota, and viruses in the gut. Viruses 2018, 10, 96. [Google Scholar] [CrossRef] [Green Version]
  19. Uchiyama, R.; Chassaing, B.; Zhang, B.; Gewirtz, A.T. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. J. Infect. Dis. 2014, 210, 171–182. [Google Scholar] [CrossRef] [Green Version]
  20. Kuss, S.K.; Best, G.T.; Etheredge, C.A.; Pruijssers, A.J.; Frierson, J.M.; Hooper, L.V.; Dermody, T.S.; Pfeiffer, J.K. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 2011, 334, 249–252. [Google Scholar] [CrossRef] [Green Version]
  21. Jones, M.K.; Watanabe, M.; Zhu, S.; Graves, C.L.; Keyes, L.R.; Grau, K.R.; Gonzalez-Hernandez, M.B.; Iovine, N.M.; Wobus, C.E.; Vinjé, J.; et al. Enteric bacteria promote human and mouse norovirus infection of B cells. Science 2014, 346, 755–759. [Google Scholar] [CrossRef] [Green Version]
  22. Pfeiffer, J.K.; Virgin, H.W. Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine. Science 2016, 351, aad5872. [Google Scholar] [CrossRef] [Green Version]
  23. Kennedy, E.A.; King, K.Y.; Baldridge, M.T. Mouse microbiota models: Comparing germ-free mice and antibiotics treatment as tools for modifying gut bacteria. Front. Physiol. 2018, 9, 1534. [Google Scholar] [CrossRef] [Green Version]
  24. Harris, V.C.; Haak, B.W.; Handley, S.A.; Jiang, B.; Velasquez, D.E.; Hykes, B.L., Jr.; Droit, L.; Berbers, G.A.M.; Kemper, E.M.; van Leeuwen, E.M.M.; et al. Effect of antibiotic-mediated microbiome modulation on rotavirus vaccine immunogenicity: A human, randomized-control proof-of-concept trial. Cell Host Microbe 2018, 24, 197–207.e4. [Google Scholar] [CrossRef] [Green Version]
  25. Barton, E.S.; White, D.W.; Cathelyn, J.S.; Brett-McClellan, K.A.; Engle, M.; Diamond, M.S.; Miller, V.L.; Virgin, H.W. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 2007, 447, 326–329. [Google Scholar] [CrossRef]
  26. Shi, Z.; Gewirtz, A.T. Together forever: Bacterial-viral interactions in infection and immunity. Viruses 2018, 10, 122. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Shi, Z.; Zou, J.; Zhang, Z.; Zhao, X.; Noriega, J.; Zhang, B.; Zhao, C.; Ingle, H.; Bittinger, K.; Mattei, L.M.; et al. Segmented filamentous bacteria prevent and cure rotavirus infection. Cell 2019, 179, 644–658.e13. [Google Scholar] [CrossRef]
  28. Zhang, Z.; Zou, J.; Shi, Z.; Zhang, B.; Etienne-Mesmin, L.; Wang, Y.; Shi, X.; Shao, F.; Chassaing, B.; Gewirtz, A.T. IL-22-induced cell extrusion and IL-18-induced cell death prevent and cure rotavirus infection. Sci. Immunol. 2020, 5, eabd2876. [Google Scholar] [CrossRef] [PubMed]
  29. Engevik, M.A.; Banks, L.D.; Engevik, K.A.; Chang-Graham, A.L.; Perry, J.L.; Hutchinson, D.S.; Ajami, N.J.; Petrosino, J.F.; Hyser, J.M. Rotavirus infection induces glycan availability to promote ileum-specific changes in the microbiome aiding rotavirus virulence. Gut Microbes 2020, 11, 1324–1347. [Google Scholar] [CrossRef]
  30. Mathew, S.; Smatti, M.K.; Al Ansari, K.; Nasrallah, G.K.; Al Thani, A.A.; Yassine, H.M. Mixed viral-bacterial infections and their effects on gut microbiota and clinical illnesses in children. Sci. Rep. 2019, 9, 865. [Google Scholar] [CrossRef] [Green Version]
  31. Harris, V.C. The significance of the intestinal microbiome for vaccinology: From correlations to therapeutic applications. Drugs 2018, 78, 1063–1072. [Google Scholar] [CrossRef] [Green Version]
  32. Harris, V.; Ali, A.; Fuentes, S.; Korpela, K.; Kazi, M.; Tate, J.; Parashar, U.; Wiersinga, W.J.; Giaquinto, C.; de Weerth, C.; et al. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan. Gut Microbes 2018, 9, 93–101. [Google Scholar] [CrossRef] [PubMed]
  33. Harris, V.C.; Armah, G.; Fuentes, S.; Korpela, K.E.; Parashar, U.; Victor, J.C.; Tate, J.; de Weerth, C.; Giaquinto, C.; Wiersinga, W.J.; et al. Significant correlation between the infant gut microbiome and rotavirus vaccine response in rural Ghana. J. Infect. Dis. 2017, 215, 34–41. [Google Scholar] [CrossRef]
  34. Fix, J.; Chandrashekhar, K.; Perez, J.; Bucardo, F.; Hudgens, M.G.; Yuan, L.; Twitchell, E.; Azcarate-Peril, M.A.; Vilchez, S.; Becker-Dreps, S. Association between gut microbiome composition and rotavirus vaccine response among Nicaraguan infants. Am. J. Trop. Med. Hyg. 2020, 102, 213–219. [Google Scholar] [CrossRef]
  35. Kim, A.H.; Hogarty, M.P.; Harris, V.C.; Baldridge, M.T. The complex interactions between rotavirus and the gut microbiota. Front. Cell Infect. Microbiol. 2021, 10, 586751. [Google Scholar] [CrossRef]
  36. Desselberger, U. Differences of rotavirus vaccine effectiveness by country: Likely causes and contributing factors. Pathogens 2017, 6, 65. [Google Scholar] [CrossRef] [Green Version]
  37. Parker, E.P.; Ramani, S.; Lopman, B.A.; Church, J.A.; Iturriza-Gómara, M.; Prendergast, A.J.; Grassly, N.C. Causes of impaired oral vaccine efficacy in developing countries. Future Microbiol. 2018, 13, 97–118. [Google Scholar] [CrossRef] [PubMed]
  38. Twitchell, E.L.; Tin, C.; Wen, K.; Zhang, H.; Becker-Dreps, S.; Azcarate-Peril, M.A.; Vilchez, S.; Li, G.; Ramesh, A.; Weiss, M.; et al. Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs. Gut Pathog. 2016, 8, 51. [Google Scholar] [CrossRef] [Green Version]
  39. Kumar, A.; Vlasova, A.N.; Deblais, L.; Huang, H.C.; Wijeratne, A.; Kandasamy, S.; Fischer, D.D.; Langel, S.N.; Paim, F.C.; Alhamo, M.A.; et al. Impact of nutrition and rotavirus infection on the infant gut microbiota in a humanized pig model. BMC Gastroenterol. 2018, 18, 93. [Google Scholar] [CrossRef] [Green Version]
  40. Magwira, C.A.; Taylor, M.B. Composition of gut microbiota and its influence on the immunogenicity of oral rotavirus vaccines. Vaccine 2018, 36, 3427–3433. [Google Scholar] [CrossRef] [PubMed]
  41. Koh, A.; De Vadder, F.; Kovatcheva-Datchary, P.; Bäckhed, F. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell 2016, 165, 1332–1345. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Yang, W.; Xiao, Y.; Huang, X.; Chen, F.; Sun, M.; Bilotta, A.J.; Xu, L.; Lu, Y.; Yao, S.; Zhao, Q.; et al. Microbiota metabolite short-chain fatty acids facilitate mucosal adjuvant activity of cholera toxin through GPR43. J. Immunol. 2019, 203, 282–292. [Google Scholar] [CrossRef] [PubMed]
  43. Yamaguchi, T.; Tsuji, S.; Akagawa, S.; Akagawa, Y.; Kino, J.; Yamanouchi, S.; Kimata, T.; Hashiyada, M.; Akane, A.; Kaneko, K. Clinical significance of probiotics for children with idiopathic nephrotic syndrome. Nutrients 2021, 13, 365. [Google Scholar] [CrossRef] [PubMed]
  44. Agus, A.; Planchais, J.; Sokol, H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe 2018, 23, 716–724. [Google Scholar] [CrossRef] [Green Version]
  45. Williams, B.B.; Van Benschoten, A.H.; Cimermancic, P.; Donia, M.S.; Zimmermann, M.; Taketani, M.; Ishihara, A.; Kashyap, P.C.; Fraser, J.S.; Fischbach, M.A. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe 2014, 16, 495–503. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Devlin, A.S.; Marcobal, A.; Dodd, D.; Nayfach, S.; Plummer, N.; Meyer, T.; Pollard, K.S.; Sonnenburg, J.L.; Fischbach, M.A. Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota. Cell Host Microbe 2016, 20, 709–715. [Google Scholar] [CrossRef] [Green Version]
  47. Shimada, Y.; Kinoshita, M.; Harada, K.; Mizutani, M.; Masahata, K.; Kayama, H.; Takeda, K. Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. PLoS ONE 2013, 8, e80604. [Google Scholar]
  48. Yano, J.M.; Yu, K.; Donaldson, G.P.; Shastri, G.G.; Ann, P.; Ma, L.; Nagler, C.R.; Ismagilov, R.F.; Mazmanian, S.K.; Hsiao, E.Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015, 161, 264–276. [Google Scholar] [CrossRef] [Green Version]
  49. Barcik, W.; Wawrzyniak, M.; Akdis, C.A.; O’Mahony, L. Immune regulation by histamine and histamine-secreting bacteria. Curr. Opin. Immunol. 2017, 48, 108–113. [Google Scholar] [CrossRef]
  50. Borbet, T.C.; Zhang, X.; Müller, A.; Blaser, M.J. The role of the changing human microbiome in the asthma pandemic. J. Allergy Clin. Immunol. 2019, 144, 1457–1466. [Google Scholar] [CrossRef]
  51. Koh, A.; Molinaro, A.; Ståhlman, M.; Khan, M.T.; Schmidt, C.; Mannerås-Holm, L.; Wu, H.; Carreras, A.; Jeong, H.; Olofsson, L.E.; et al. Microbially produced imidazole propionate impairs insulin signaling through mTORC1. Cell 2018, 175, 947–961.e17. [Google Scholar] [CrossRef] [Green Version]
  52. Molinaro, A.; Lassen, P.B.; Henricsson, M.; Wu, H.; Adriouch, S.; Belda, E.; Chakaroun, R.; Nielsen, T.; Bergh, P.O.; Rouault, C.; et al. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology. Nat. Commun. 2020, 11, 5881. [Google Scholar]
  53. Maini Rekdal, V.; Bess, E.N.; Bisanz, J.E.; Turnbaugh, P.J.; Balskus, E.P. Discovery and inhibition of an interspecies gut bacterial pathway for levodopa metabolism. Science 2019, 364, eaau6323. [Google Scholar] [CrossRef] [Green Version]
  54. van Kessel, S.P.; Frye, A.K.; El-Gendy, A.O.; Castejon, M.; Keshavarzian, A.; van Dijk, G.; El Aidy, S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease. Nat. Commun. 2019, 10, 310. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Wypych, T.P.; Pattaroni, C.; Perdijk, O.; Yap, C.; Trompette, A.; Anderson, D.; Creek, D.J.; Harris, N.L.; Marsland, B.J. Microbial metabolism of L-tyrosine protects against allergic airway inflammation. Nat. Immunol. 2021, 22, 279–286. [Google Scholar] [CrossRef] [PubMed]
  56. Singh, A.K.; Cabral, C.; Kumar, R.; Ganguly, R.; Rana, H.K.; Gupta, A.; Lauro, M.R.; Carbone, C.; Reis, F.; Pandey, A.K. Beneficial effects of dietary polyphenols on gut microbiota and strategies to improve delivery efficiency. Nutrients 2019, 11, 2216. [Google Scholar]
  57. Buffie, C.G.; Bucci, V.; Stein, R.R.; McKenney, P.T.; Ling, L.; Gobourne, A.; No, D.; Liu, H.; Kinnebrew, M.; Viale, A.; et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 2015, 517, 205–208. [Google Scholar] [CrossRef] [Green Version]
  58. Wahlström, A.; Sayin, S.I.; Marschall, H.U.; Bäckhed, F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016, 24, 41–50. [Google Scholar] [CrossRef] [Green Version]
  59. Chen, S.; Henderson, A.; Petriello, M.C.; Romano, K.A.; Gearing, M.; Miao, J.; Schell, M.; Sandoval-Espinola, W.J.; Tao, J.; Sha, B.; et al. Trimethylamine N-oxide binds and activates PERK to promote metabolic dysfunction. Cell Metab. 2019, 30, 1141–1151.e5. [Google Scholar] [CrossRef]
  60. Shan, Z.; Sun, T.; Huang, H.; Chen, S.; Chen, L.; Luo, C.; Yang, W.; Yang, X.; Yao, P.; Cheng, J.; et al. Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes. Am. J. Clin. Nutr. 2017, 106, 888–894. [Google Scholar] [CrossRef] [Green Version]
  61. Tang, W.H.; Kitai, T.; Hazen, S.L. Gut microbiota in cardiovascular health and disease. Circ. Res. 2017, 120, 1183–1196. [Google Scholar] [CrossRef] [Green Version]
  62. An, D.; Oh, S.F.; Olszak, T.; Neves, J.F.; Avci, F.Y.; Erturk-Hasdemir, D.; Lu, X.; Zeissig, S.; Blumberg, R.S.; Kasper, D.L. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 2014, 156, 123–133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  63. Brown, E.M.; Ke, X.; Hitchcock, D.; Jeanfavre, S.; Avila-Pacheco, J.; Nakata, T.; Arthur, T.D.; Fornelos, N.; Heim, C.; Franzosa, E.A.; et al. Bacteroides-derived sphingolipids are critical for maintaining intestinal homeostasis and symbiosis. Cell Host Microbe 2019, 25, 668–680.e7. [Google Scholar] [CrossRef] [PubMed]
  64. Deehan, E.C.; Yang, C.; Perez-Muñoz, M.E.; Nguyen, N.K.; Cheng, C.C.; Triador, L.; Zhang, Z.; Bakal, J.A.; Walter, J. Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production. Cell Host Microbe 2020, 27, 389–404.e6. [Google Scholar] [CrossRef] [PubMed]
  65. den Besten, G.; van Eunen, K.; Groen, A.K.; Venema, K.; Reijngoud, D.J.; Bakker, B.M. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 2013, 54, 2325–2340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  66. Rangan, K.J.; Hang, H.C. Biochemical mechanisms of pathogen restriction by intestinal bacteria. Trends Biochem. Sci. 2017, 42, 887–898. [Google Scholar] [CrossRef]
  67. Rodriguez, D.M.; Benninghoff, A.D.; Aardema, N.D.J.; Phatak, S.; Hintze, K.J. Basal diet determined long-term composition of the gut microbiome and mouse phenotype to a greater extent than fecal microbiome transfer from lean or obese human donors. Nutrients 2019, 11, 1630. [Google Scholar] [CrossRef] [Green Version]
  68. Kovatcheva-Datchary, P.; Shoaie, S.; Lee, S.; Wahlström, A.; Nookaew, I.; Hallen, A.; Perkins, R.; Nielsen, J.; Bäckhed, F. Simplified intestinal microbiota to study microbe-diet-host interactions in a mouse model. Cell Rep. 2019, 26, 3772–3783.e6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  69. Chen, R.Y.; Mostafa, I.; Hibberd, M.C.; Das, S.; Mahfuz, M.; Naila, N.N.; Islam, M.M.; Huq, S.; Alam, M.A.; Zaman, M.U.; et al. A microbiota-directed food intervention for undernourished children. N. Engl. J. Med. 2021, 384, 1517–1528. [Google Scholar] [CrossRef]
  70. Harris, V.C.; Haak, B.W.; van Hensbroek, M.B.; Wiersinga, W.J. The intestinal microbiome in infectious diseases: The clinical relevance of a rapidly emerging field. Open Forum Infect. Dis. 2017, 4, ofx144. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  71. Giovanni, M.Y.; Schneider, J.S.; Calder, T.; Fauci, A.S. Refocusing human microbiota research in infectious and immune-mediated diseases: Advancing to the next stage. J. Infect. Dis. 2020, 224, 5–8. [Google Scholar] [CrossRef]
  72. Simon, M.C.; Reinbeck, A.L.; Wessel, C.; Heindirk, J.; Jelenik, T.; Kaul, K.; Arreguin-Cano, J.; Strom, A.; Blaut, M.; Bäckhed, F.; et al. Distinct alterations of gut morphology and microbiota characterize accelerated diabetes onset in nonobese diabetic mice. J. Biol. Chem. 2020, 295, 969–980. [Google Scholar] [CrossRef]
  73. Gupta, A.; Osadchiy, V.; Mayer, E.A. Brain-gut-microbiome interactions in obesity and food addiction. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 655–672. [Google Scholar] [CrossRef] [PubMed]
  74. Ezzaidi, N.; Zhang, X.; Coker, O.O.; Yu, J. New insights and therapeutic implication of gut microbiota in non-alcoholic fatty liver disease and its associated liver cancer. Cancer Lett. 2019, 459, 186–191. [Google Scholar] [CrossRef]
  75. Jiang, L.; Stärkel, P.; Fan, J.G.; Fouts, D.E.; Bacher, P.; Schnabl, B. The gut mycobiome: A novel player in chronic liver diseases. J. Gastroenterol. 2021, 56, 1–11. [Google Scholar] [CrossRef]
  76. Brunt, V.E.; Casso, A.G.; Gioscia-Ryan, R.A.; Sapinsley, Z.J.; Ziemba, B.P.; Clayton, Z.S.; Bazzoni, A.E.; VanDongen, N.S.; Richey, J.J.; Hutton, D.A.; et al. Gut microbiome-derived metabolite trimethylamine N-oxide induces aortic stiffening and increases systolic blood pressure with aging in mice and humans. Hypertension 2021, 78, 499–511. [Google Scholar] [CrossRef] [PubMed]
  77. Garshick, M.S.; Nikain, C.; Tawil, M.; Pena, S.; Barrett, T.J.; Wu, B.G.; Gao, Z.; Blaser, M.J.; Fisher, E.A. Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice. Sci. Rep. 2021, 11, 8966. [Google Scholar] [CrossRef]
  78. Patnode, M.L.; Beller, Z.W.; Han, N.D.; Cheng, J.; Peters, S.L.; Terrapon, N.; Henrissat, B.; Le Gall, S.; Saulnier, L.; Hayashi, D.K.; et al. Interspecies competition impacts targeted manipulation of human gut bacteria by fiber-derived glycans. Cell 2019, 179, 59–73.e13. [Google Scholar] [CrossRef] [PubMed]
  79. Raman, A.S.; Gehrig, J.L.; Venkatesh, S.; Chang, H.W.; Hibberd, M.C.; Subramanian, S.; Kang, G.; Bessong, P.O.; Lima, A.A.M.; Kosek, M.N.; et al. A sparse covarying unit that describes healthy and impaired human gut microbiota development. Science 2019, 365, eaau4735. [Google Scholar] [CrossRef] [Green Version]
  80. Huang, H.C.; Vlasova, A.N.; Kumar, A.; Kandasamy, S.; Fischer, D.D.; Deblais, L.; Paim, F.C.; Langel, S.N.; Alhamo, M.A.; Rauf, A.; et al. Effect of antibiotic, probiotic, and human rotavirus infection on colonisation dynamics of defined commensal microbiota in a gnotobiotic pig model. Benef. Microbes 2018, 9, 71–86. [Google Scholar] [CrossRef]
  81. Kandasamy, S.; Vlasova, A.N.; Fischer, D.; Kumar, A.; Chattha, K.S.; Rauf, A.; Shao, L.; Langel, S.N.; Rajashekara, G.; Saif, L.J. Differential effects of Escherichia coli Nissle and Lactobacillus rhamnosus Strain GG on human rotavirus binding, infection, and B cell immunity. J. Immunol. 2016, 196, 1780–1789. [Google Scholar] [CrossRef] [Green Version]
  82. Valdez, Y.; Brown, E.M.; Finlay, B.B. Influence of the microbiota on vaccine effectiveness. Trends Immunol. 2014, 35, 526–537. [Google Scholar] [CrossRef]
  83. Villena, J.; Vizoso-Pinto, M.G.; Kitazawa, H. Intestinal innate antiviral immunity and immunobiotics: Beneficial effects against rotavirus infection. Front. Immunol. 2016, 7, 563. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Wang, H.; Gao, K.; Wen, K.; Allen, I.C.; Li, G.; Zhang, W.; Kocher, J.; Yang, X.; Giri-Rachman, E.; Li, G.H.; et al. Lactobacillus rhamnosus GG modulates innate signaling pathway and cytokine responses to rotavirus vaccine in intestinal mononuclear cells of gnotobiotic pigs transplanted with human gut microbiota. BMC Microbiol. 2016, 16, 109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Zhang, W.; Azevedo, M.S.; Wen, K.; Gonzalez, A.; Saif, L.J.; Li, G.; Yousef, A.E.; Yuan, L. Probiotic Lactobacillus acidophilus enhances the immunogenicity of an oral rotavirus vaccine in gnotobiotic pigs. Vaccine 2008, 26, 3655–3661. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  86. Zimmermann, P.; Curtis, N. The influence of the intestinal microbiome on vaccine responses. Vaccine 2018, 36, 4433–4439. [Google Scholar] [CrossRef]
  87. Barba-Vidal, E.; Roll, V.F.B.; Manzanilla, E.G.; Torrente, C.; Muñoz, J.A.M.; Pérez, J.F.; Martín-Orúe, S.M. Blood parameters as biomarkers in a Salmonella spp. disease model of weaning piglets. PLoS ONE 2017, 12, e0186781. [Google Scholar]
  88. Huang, Y.F.; Liu, P.Y.; Chen, Y.Y.; Nong, B.R.; Huang, I.F.; Hsieh, K.S.; Chen, K.T. Three-combination probiotics therapy in children with Salmonella and rotavirus gastroenteritis. J. Clin. Gastroenterol. 2014, 48, 37–42. [Google Scholar] [CrossRef]
  89. Kawahara, T.; Makizaki, Y.; Oikawa, Y.; Tanaka, Y.; Maeda, A.; Shimakawa, M.; Komoto, S.; Moriguchi, K.; Ohno, H.; Taniguchi, K. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors. PLoS ONE 2017, 12, e0173979. [Google Scholar] [CrossRef] [Green Version]
  90. Schnadower, D.; Tarr, P.I.; Casper, T.C.; Gorelick, M.H.; Dean, J.M.; O’Connell, K.J.; Mahajan, P.; Levine, A.C.; Bhatt, S.R.; Roskind, C.G.; et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N. Engl. J. Med. 2018, 379, 2002–2014. [Google Scholar] [CrossRef]
  91. Engevik, M.A.; Danhof, H.A.; Shrestha, R.; Chang-Graham, A.L.; Hyser, J.M.; Haag, A.M.; Mohammad, M.A.; Britton, R.A.; Versalovic, J.; Sorg, J.A.; et al. Reuterin disrupts Clostridioides difficile metabolism and pathogenicity through reactive oxygen species generation. Gut Microbes 2020, 12, 1795388. [Google Scholar] [CrossRef] [PubMed]
  92. Pandey, K.R.; Naik, S.R.; Vakil, B.V. Probiotics, prebiotics and synbiotics—A review. J. Food Sci. Technol. 2015, 52, 7577–7587. [Google Scholar] [CrossRef]
  93. Fischer, M.; Kao, D.; Kelly, C.; Kuchipudi, A.; Jafri, S.M.; Blumenkehl, M.; Rex, D.; Mellow, M.; Kaur, N.; Sokol, H.; et al. Fecal microbiota transplantation is safe and efficacious for recurrent or refractory Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm. Bowel. Dis. 2016, 22, 2402–2409. [Google Scholar] [CrossRef] [Green Version]
  94. van Nood, E.; Vrieze, A.; Nieuwdorp, M.; Fuentes, S.; Zoetendal, E.G.; de Vos, W.M.; Visser, C.E.; Kuijper, E.J.; Bartelsman, J.F.; Tijssen, J.G.; et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 2013, 368, 407–415. [Google Scholar] [CrossRef] [Green Version]
  95. Tixier, E.N.; Verheyen, E.; Luo, Y.; Grinspan, L.T.; Du, C.H.; Ungaro, R.C.; Walsh, S.; Grinspan, A.M. Systematic review with meta-analysis: Fecal microbiota transplantation for severe or fulminant Clostridioides difficile. Dig. Dis. Sci. 2021. [Google Scholar] [CrossRef] [PubMed]
  96. Allegretti, J.R.; Mullish, B.H.; Kelly, C.; Fischer, M. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet 2019, 394, 420–431. [Google Scholar] [CrossRef]
Table
Table 1. * Gut microbe fermentation products of carbohydrates, proteins, and dietary polyphenols.
Table 1. * Gut microbe fermentation products of carbohydrates, proteins, and dietary polyphenols.
MetabolitePathwayBacterial Species (Selected)EffectsReferences
Acetate,Starch and amino acid fermentationBifidobacterium spp.Anti-inflammatory[7,43,64,65]
propionate,Bacteroides spp.Stronger immune responses
succinate,Coprococcus spp.
butyrate
Short-chain fatty acids Campylobacter spp.Adjuvant for cholera vaccine[42]
Clostridium spp.
Eubacterium spp.
KynurenineTryptophan fermentationFusobacterium spp.Neurological disorder[44,45]
Pseudomonas spp.
Indoles Bacteroides spp.Protection from colitis[47]
E. coli [44,46]
Tryptamine Clostridium sporogenesTreatment of migraine[45]
SerotoninInduction of hostClostridium spp.Gut motility[48]
Platelet functions
HistamineHistidine fermentationE. coli, LactobacillusImmunpathology[49,50]
LactobacillusAsthma
Imidazole propionate Lactobacillus spp.Risk of T2D **[51,52]
Streptococcus spp.
DopamineDOPAEnterococcusTreatment of Parkinson’s disease[53,54]
metabolismHelicobacter
P-cresolTyrosine and phenylalanine fermentationClostridium spp.Reduction of airways inflammation[55]
PolyphenolsDietary and bacterialVarious spp.Anti-inflammatory[56]
Bile acidsSecondaryVarious spp.Risk of obesity[57,58]
Protection against Cl. diff.
Trimethylamine-N oxideCholine metabolismVarious spp.Risk of atherosclerosis[59,60,61]
Risk of T2D
SphingolipidsLipid metabolismBacteroides spp.Maintenance of gut homeostasis[62,63]
* Adapted from [7,8,66]. ** T2D: type 2 diabetes.
Table
Table 2. Topics of future research on gut microbiota.
Table 2. Topics of future research on gut microbiota.
Molecular Biology
Interrelationship of host and gut microbiota metabolism and influence of nutrition
Identification of metabolic pathways of gut microbiota determining strong acquired immune responses
Optimization of nutrition to favor the replication of microbiota considered relevant for strong immune responses and general health promotion
Influence of joint microbiome–host metabolome on health and disease
Pathophysiology
Factors determining eubiotic homeostasis and the development of gut microbial dysbiosis
Relationship of defined dysbioses with clinical phenotypes of hosts
Identification of conditions in low-income countries affecting an unfavorablecomposition of the gut microbiome
Effect of probiotics on immune responses
Identification of metabolites of microbes used as probiotics favoring the development of strong immune responses
Reliability of animal models for the development of human probiotics
Optimization of microbiome in human extended programs of immunization
Identification of probiotics for use in childhood vaccination programs in low- and middle-income countries
Identification of gut microbes universally correlated with optimal immune responses, and of others correlated with insufficient immune responses
Dependence of probiotics on the underlying microbiome composition in infants in countries of different socioeconomic standards
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Desselberger, U. Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases. Viruses 2021, 13, 1601. https://doi.org/10.3390/v13081601

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Desselberger U. Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases. Viruses. 2021; 13(8):1601. https://doi.org/10.3390/v13081601

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