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Microbiota of the Stomach and Small Intestine

The human gastrointestinal (GI) tract is characterized by distinct physicochemical conditions that shape its microbial communities. Among these, the stomach presents a particularly challenging environment for microbial colonization due to its highly acidic pH, ranging from 1 to 3. This extreme acidity effectively limits microbial density. However, certain acid-tolerant microorganisms are capable of surviving in this niche. Notably, Helicobacter pylori can colonize the gastric mucosa,...
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The large intestine hosts the most densely populated microbial ecosystem in the human body. This complex community primarily consists of anaerobic bacteria, with Bacillota (formerly Firmicutes) and Bacteroidota (formerly Bacteroidetes) as the predominant groups. The distribution of these microbes varies along different sections of the large intestine, influenced by local environmental factors such as oxygen availability and nutrient composition.The cecum, located at the beginning of the large...
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The human gut microbiome includes a diverse array of microbial species, including beneficial commensals and opportunistic pathogens, which interact to support host health. These microbes contribute to essential functions such as nutrient metabolism, immune system modulation, and maintenance of intestinal barrier integrity. However, disruptions to this equilibrium—referred to as dysbiosis—can have widespread physiological consequences.Dysbiosis is often characterized by reduced microbial...
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Diet posttranslationally modifies the mouse gut microbial proteome to modulate renal function.

Lior Lobel1, Y Grace Cao1, Kathrin Fenn1

  • 1Departments of Immunology and Infectious Diseases and Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

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Dietary sulfur amino acids can modify gut microbes to reduce uremic toxins and slow chronic kidney disease (CKD) progression in mice. This approach tunes microbial function via posttranslational modification without changing the gut microbiome composition.

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Area of Science:

  • Microbiology
  • Nephrology
  • Biochemistry

Background:

  • Chronic kidney disease (CKD) is linked to gut microbiota alterations, but mechanisms are unclear.
  • Dietary protein intake boosts gut bacterial production of hydrogen sulfide (H2S), indole, and indoxyl sulfate, which are linked to uremic toxins.
  • Hydrogen sulfide (H2S) has diverse physiological roles, some involving posttranslational modifications.

Purpose of the Study:

  • To investigate how dietary sulfur amino acids affect gut microbiota function in a mouse model of CKD.
  • To explore the role of posttranslational modification in mediating the effects of diet on microbial uremic toxin production.
  • To determine if modulating microbial activity can ameliorate CKD progression.

Main Methods:

  • Utilized a mouse model of chronic kidney disease (CKD).
  • Administered a diet rich in sulfur amino acids.
  • Analyzed microbial tryptophanase activity and its posttranslational modifications.
  • Assessed the impact on uremic toxin production and CKD progression.

Main Results:

  • A high sulfur amino acid diet induced posttranslational modifications in microbial tryptophanase.
  • These modifications decreased the activity of tryptophanase, reducing uremic toxin production.
  • Diet-induced modulation of microbial function ameliorated CKD progression in the mouse model.
  • Microbial community composition remained unchanged despite functional alterations.

Conclusions:

  • Diet can modulate gut microbiota function through posttranslational modification of microbial enzymes.
  • Targeting microbial enzyme activity, rather than community composition, offers a strategy to reduce uremic toxins.
  • Dietary interventions hold potential for managing chronic kidney disease (CKD) by tuning gut microbiota function.