intestinal bacteria (flora)

Introduction

Bacteria present in the intestinal tract.

Also see normal microbial flora.

Classification

• enterotypes
  • Bacteroides enterotype (B-type)
  • Ruminococcaceae enterotype (R-type)
  • Prevotella enterotype (P-type)

* B-type with lower stool energy density, shorter intestinal transit times, & lower alpha-diversity compared to R-type

* P-type intermediate between B-type & R-type

* B-type individuals heavier than R-type

Epidemiology

• men who have sex with men have Prevotella-dominant microbiomes
  • Prevotella-dominant microbiome associated with HIV1 infection
• other men have Bacteroides-dominant microbiomes
• Veillonella atypica found in higher concentrations in intestines of marathon runners than in nonathletes
• in middle-age subjects intestinal bacteria were associated with cognitive effects
  • Barnesiella with benefit in cognitive testing including
    • digital symbol substitution test
    • category fluency
  • Lachnospiraceae FCS020 group with benefit on digital symbol substitution test
  • Sutterella with poorer performance on Montreal Cognitive Assessment

Pathology

• intestinal flora appear to be implicated in obesity, dyslipidemia, & insulin resistance
• oral antibiotics reduce microbiome diversity in feces
  • specifically, bacteria that produce butyrate* are reduced
    • clindamycin reduces microbiome diversity for up to 4 months
    • ciprofloxacin reduces microbiome diversity for up to 12 months
• 24% of non-antibiotic drugs, members of all therapeutic classes, inhibit growth of at least one intestinal strain in vitro
  • antipsychotics, other psychoactive agents, proton-pump inhibitors, antineoplastics, & hormones over-represented
• bacteria resistant to various antibiotics also were resistant to inhibiting effects of nonantibiotics
• bacterial mutations that eject antibiotics from bacterial cells also ejected some nonantibiotic drugs
• animal-based diets increase the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, Bacteroides)
  • activity of Bilophila wadsworthia associated with an animal-based diet may play a role in triggering inflammatory bowel disease
• plant-based diets increase the abundance of Firmicutes (Roseburia, Eubacterium rectale, Ruminococcus bromii) that metabolize dietary plant polysaccharides
• Fusobacterium nucleatum appears to be implicated in colorectal carcinoma
• Bacteroides species present in intestinal flora of infants may suppress development of tolerance to self-antigens & increase risk of type 1 diabetes
• gut microbial viversity diminishes with increased frailty in community-dwelling elderly & in long-term care residents
• intestinal bacteria of the Ruminococcaceae family & Clostridiales order, & especially of the genus Faecalibacterium confer better response to anti-PD-1 immunotherapy in patients with melanoma
  • intestinal bacteria of the Bacteroidales order confer worse response to anti-PD-1 immunotherapy
• responders to immunotherapy for metastatic melanoma with gut microbiome abundant in 8 bacterial species
• recent antibiotics confer worse response in patients with lung cancer, renal cell carcinoma, & urothelial cancer undergoing anti-PD-1 immunotherapy
  • abundance of Akkermansia muciniphila associated with the best clinical outcomes
• dietary salt decreases intestinal Lactobacilli in mice & humans & increases blood pressure
• elevated levels of phenylacetylglutamine, a byproduct of microbial break down dietary protein, increases risk of heart failure & severity, & risk of myocardial infarction, stroke & death
• Enterococcus gallinarum may be associated with lupus
• the microbiome may influence development of both obesity & type 2 diabetes,1 both of which are atherogenic
• intestinal bacteria produce neuroactive molecules as well as molecules that influence cells to produce neuroactive agents
  • metabolism of intestinal bacteria appear to be linked to functional status & mood, possibly influencing depression
  • 47 specific bacterial species, 3 specific bacteriophages, & 50 fecal metabolites are significantly associated with major depression
  • among the 50 metabolites gamma-aminobutyrate, phenylalanine & tryptophan enter the blood from the gut, affect neurochemistry, & have been implicated in major depression

* butyrate-producing bacteria are linked to lower inflammation, carcinogenesis, & oxidative stress in the gut

Genetics

• for some bacteria, i.e. Bacteroidetes, environmental influences are much greater than genomic influences
• for bacteria, i.e. Christensenellaceae, the opposite was true
  • Christensenellaceae appear to protect against obesity

Pharmacology

• some bacteria can store a drug without chemically modifying it
  • other bacteria chemically modify it to make it more or less bioactive
• a drug can affect a patient's gut bacteria, their number & function
• accumulation of a drug within a strain of bacteria can alter the growth rate of those bacteria
• a drug can change molecules secreted by bacteria, including hormones, neurotransmitters, & inflammatory molecules
• communities of intestinal bacteria influence response to checkpoint inhibitors in patients with non-small cell lung carcinoma

Physiology

• small intestine
  • Lactobacillus spp (3+)
  • Bacteroides spp (3+)
  • Clostridium spp (2+)
  • Mycobacterium spp (2+)
  • Enterococci (2+)
  • Enterobacteriaceae (2+)
• large intestine
  • Bacteroides spp (4+)
  • Fusobacterium spp
    • Fusobacterium nucleatum may be increased in patients with colon cancer
  • Ruminococcaceae
    • Ruminococcus (neuroprotective)
    • Butyricicoccus (neuroprotective)
  • Clostridium spp (4+)
  • Peptostreptococcus spp (4+)
  • Enterobacteriaceae (4+)
    • Escherichia coli
    • Klebsiella spp
    • Proteus spp
  • Lactobacillus spp (3+)
  • Enterococci (2+)
  • Streptococci
  • Pseudomonas spp (1+)
  • Acinetobacter spp
  • coagulase-negative staphylococci (1+)
  • Staphylococcus aureus (1+)
  • Mycobacterium spp (1+)
  • Actinomyces spp

* the adherens junctions of the intestinal epithelium provide a barrier to the movement of intestinal bacteria from the gut lumen into tissues & the circulation

* exercise increases diversity of gut microbiota

• diet also plays a role

* antibiotic or probiotic use affects gut microbiota

* fecal transplantation alters gut microbiota

* > 400 species

* estimated weight of microbial flora in human gut is 1-1.4 kg

* an infant's intestinal flora is strongly influenced by the mother's intestinal flora during vaginal delivery

* in life a person's intestinal flora is influenced by diet & lifestyle

* gut microbiota similiar in health aged & health young Chinese

Comparative biology

• nonpathogenic Clostridia (17 strains) normally found in human intestinal flora can suppress immunologically mediated disease in mice
  • the Clostridial strains induce CD4+FOXP3+ regulatory T-cells
  • promise for treatment of inflammation & allergy
• fecal transplantation from mice with anti-melanoma immunity augments responses to anti-PDL1 immunotherapy
  • augmented response apparently conferred by Bifidobacterium
• probiotic therapy with Bifidobacterium species prevented or ameliorated autoimmune colitis in a mouse melanoma model
  • effect mediated by regulatory T cells (CTLA4 inhibition)
• fecal transplantation into mice from patients treated with ipilimumab enhances responses of mice to anti-CTLA4 therapy
• high-glycemic index diets worsen macular deneration in mice
  • low glycemic index diets arrest progession of macular deneration in mice
  • changes dependent on changes in the gut microbiome
• lipopolysaccharide (LPS) produced by gram-negative bacteria can penetrate the gut mucosa during inflammation & can enter the circulation in mice
  • LPS stimulates TKR4 on the endothelial wall of cerebral blood vessels & this triggers morphologic changes that evolve into serebral cavernous malformations, strokes & seizures
• Enterococcus gallinarum can penetrate intestinal epithelium, translocate to mesenteric lymph nodes & liver, resulting in condition similar to systemic lupus erythematosus in mice
• prebiotic (10% oligofructose-enriched inulin) fed to mice altered gut microbiota in young & middle-aged mice with changes correlating with fecal metabolites; Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice, reduction of infiltration of monocytes inro brain & a reversal in ageing-related increases in a subset of activated microglia
• microbiome-dependent production of endocannabinoid metabolites in the gut stimulates activity of TRPV1-expressing sensory neurons thus elevating dopamine levels in the ventral striatum during exercise in mice
  • this increases the desire of mice to exercise
• in 3xTg-AD mice, Klebsiella pneumoniae can translocate from the gut to the bloodstream by penetrating the gut epithelial barrier & susequently infiltrate the brain by penetrating the blood-brain barrier

Notes

• Lactobacillus rhamnosus GG strain may benefit memory
• Prevotella may negatively impact memory
• for resistant isolates of enteric bacteria, report to EntericBacteria@cdc.gov

More general terms

• bacteria
• intestinal flora; gut microbiome

Additional terms

• intestinal epithelium
• small intestinal bacterial overgrowth

Component of

• microbial flora (microbiome)