Metabolic functions of the human gut microbiota: the role of metalloenzymes

Rajakovich, Lauren J.; Balskus, Emily P.

doi:10.1039/c8np00074c

Cited by 70 publications

(60 citation statements)

References 391 publications

(549 reference statements)

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“…The GI tract hosts a unique, yet, complex microbial communities that provide a distinct platform for many metabolic interactions 99 . One major element of this biochemical output comprises proteases 99 . Serine proteases represent an important class of enzymes for prokaryotes 100 .…”

Section: Gut Microbial Serine Proteasesmentioning

confidence: 99%

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

et al. 2020

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Serine proteases have been long recognized to coordinate many physiological processes and play key roles in regulating the inflammatory response. Accordingly, their dysregulation has been regularly associated with several inflammatory disorders and suggested as a central mechanism in the pathophysiology of digestive inflammation. So far, studies addressing the proteolytic homeostasis in the gut have mainly focused on host serine proteases as candidates of interest, while largely ignoring the potential contribution of their bacterial counterparts. The human gut microbiota comprises a complex ecosystem that contributes to host health and disease. Yet, our understanding of microbially produced serine proteases and investigation of whether they are causally linked to IBD is still in its infancy. In this review, we highlight recent advances in the emerging roles of host and bacterial serine proteases in digestive inflammation. We also discuss the application of available tools in the gut to monitor disease‐related serine proteases. An exhaustive representation and understanding of such functional potential would help in closing existing gaps in mechanistic knowledge.

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Section: Gut Microbial Serine Proteasesmentioning

confidence: 99%

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

et al. 2020

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“…Over 99% of GI tract microbiota are anaerobic bacteria and they play important roles in physiological homeostasis and metabolism functions including pathogen displacement, immune system development, barrier fortification, vitamin K synthesis, and nutrient absorption; however, this is often referred to as the "forgotten organ" [25]. Moreover, they are found to involve in the microbiota-gut-brain axis bidirectionally connecting neural [26], immune [27], endocrine [28] and metabolic pathways [29,30]. Recent studies suggest that the gut microbiota play a critical role in neurodegenerative diseases including AD or various types of dementia [31,32].…”

Section: Introductionmentioning

confidence: 99%

d-glutamate and Gut Microbiota in Alzheimer’s Disease

Chang

Lin

Lane

2020

IJMS

128

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Background: An increasing number of studies have shown that the brain–gut–microbiota axis may significantly contribute to Alzheimer’s disease (AD) pathogenesis. Moreover, impaired memory and learning involve the dysfunction neurotransmission of glutamate, the agonist of the N-methyl-d-aspartate receptor and a major excitatory neurotransmitter in the brain. This systematic review aimed to summarize the current cutting-edge research on the gut microbiota and glutamate alterations associated with dementia. Methods: PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews were reviewed for all studies on glutamate and gut microbiota in dementia published up until Feb 2020. Results: Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including Bacteroides vulgatus and Campylobacter jejuni affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including Corynebacterium glutamicum, Brevibacterium lactofermentum, and Brevibacterium avium can convert l-glutamate to d-glutamate. N-methyl-d-aspartate glutamate receptor (NMDAR)-enhancing agents have been found to potentially improve cognition in AD or Parkinson’s disease patients. These findings suggest that d-glutamate (d-form glutamate) metabolized by the gut bacteria may influence the glutamate NMDAR and cognitive function in dementia patients. Conclusions: Gut microbiota and glutamate are potential novel interventions to be developed for dementia. Exploring comprehensive cognitive functions in animal and human trials with glutamate-related NMDAR enhancers are warranted to examine d-glutamate signaling efficacy in gut microbiota in patients with AD and other neurodegenerative dementias.

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“…These interactions have introduced complexity within the human gastrointestinal tract and established a wellstratified ecosystem of diversified microbes, together known as the human gut microbiome or microbiota. The gut microbiome is an essential catalyst for the successful survival of the host (Rajakovich and Balskus 2019). Any alteration in the gut bacterial composition, also termed as microbial dysbiosis could result in a number of physiological or metabolic disorders within the body which may relate to alteration in the balance between pathogenic and beneficial microbes (Colonetti et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics

Yadav

Chauhan

2020

J Appl Microbiol

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Human gut microbiome is a diversified, resilient, immuno-stabilized, metabolically active and physiologically essential component of the human body. Scientific explorations have been made to seek in-depth information about human gut microbiome establishment, microbiome functioning, microbiome succession, factors influencing microbial community dynamics and the role of gut microbiome in health and diseases. Extensive investigations have proposed the microbiome therapeutics as a futuristic medicine for various physiological and metabolic disorders. A comprehensive outlook of microbial colonization, host-microbe interactions, microbial adaptation, commensal selection and immuno-survivability is still required to catalogue the essential genetic and physiological features for the commensal engagement. Evolution of a structured human gut microbiome relies on the microbial flexibility towards genetic, immunological and physiological adaptation in the human gut. Key features for commensalism could be utilized in developing tailor-made microbiome-based therapy to overcome various physiological and metabolic disorders. This review describes the key genetics and physiological traits required for host-microbe interaction and successful commensalism to institute a human gut microbiome.

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Metabolic functions of the human gut microbiota: the role of metalloenzymes

Abstract: Metalloenzymes play central roles in metabolic functions of the human gut microbiota that are associated with host health and disease.

Cited by 70 publications

References 391 publications

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

d-glutamate and Gut Microbiota in Alzheimer’s Disease

Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics

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