see also:

• gut-brain axis and the GIT microbiome
• the oral microbiome
• clinically important bacteria

• recent research is increasingly shining a light on the many roles of the microbiome in the gut
• it appears the microbiome can modulate:
  • gut-brain bi-directional signalling and even mental health
  • inflammation - not only within the GIT but the level of systemic low grade inflammatory cytokines and related molecules
  • disease susceptibility or severity
    • “gut microbiota modulation of the gut immune system plays a significant role in the development and training of the systemic immune system and influences the outcome of extragastrointestinal diseases like influenza, HIV, diabetes, multiple sclerosis, and autoimmune arthritis, among others. For example, segmented filamentous bacteria induce the differentiation of Peyer’s patch CD4 T cells into follicular T helper cells, which enter circulation and regulate germinal center formation in auto-antibody production in systemic lymph nodes” ³⁾
• the microbiome can remove some toxins
  • Bacteroides uniformis in particular appears to have a strong ability to absorb PFAS forever toxins from the body which are then excreted in faeces
• when the gut microbiome is severely disrupted as in antibiotic therapy, there is a risk of life threatening toxic megacolon due to overgrowth of colonic Clostridium difficile
  • this requires the oro-fecal transmission of sufficient numbers of spores of a toxin-producing strain of C. difficile (usually nosocomial) within the colon of the host (unless already colonized), accompanied by their overgrowth at the expense of normal commensal microorganisms
    • 70% of newborns and infants appear to be colonized by C. difficile (lower in vaginal births as Bifidobacterium longum is more likely and are protective and negatively correlated to C. difficile colonization) however their gut appears to be resistant to the toxins - perhaps by by the absence of toxin receptors, poorly developed cellular signaling pathways because of the immature gut mucosa, or the presence of protective factors in the infantile gut such as human milk proteins which play an inhibitory role in toxin TcdA while secretory IgA has shown neutralizing activity against toxin A
    • 2-17.5% of healthy adults have asymptomatic C. difficile, protected by commensal bacterial flora while asymptomatic colonization on admission to the hospital is estimated to have a prevalence of 0.6–13% ⁴⁾
  • lysozyme (LYZ) deficiency drives vascular aging via gut dysbiosis via PI3K-Akt suppression and Lyz1 could be used as a marker for vascular aging
    • oral lysozyme (LYZ) appears to restore gut balance and reverse vascular inflammatory aging phenotypes in mice ⁵⁾
• probiotics are “Live microorganisms that, when administered in adequate amounts, confer a health benefit upon the host”
• prebiotics are “A selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-bring and health”
• “synbiotic” means the administration of a prebiotic together with a specific probiotic to enhance the engraftment and development of that specific microbe
• “psychobiotics” gut microbes which positively impact behaviour though the microbiota-gut-brain axis
• fermented foods exert profound effects on the gut-brain axis through modulation of the enteroendocrine system (EES), influencing gut hormones like serotonin, neuropeptide-Y, glucagon-like peptide 1 (GLP-1), ghrelin, and somatostatin. These hormones regulate motility, appetite, and insulin release, impacting feeding behavior. Fermented foods, rich in prebiotics and probiotics, shape the gut microbiota and enhance the production of gut hormones, particularly GLP-1. Fermented foods may alter ghrelin and leptin levels, contributing to appetite regulation. ⁶⁾
• adverse effects of food preservatives
  • food manufacturers often add preservatives to stop foods spoiling - these are often lanthipeptide “lantibiotics” - a class of bacterial chemicals which kill other bacteria but when used in food as a preservative (eg. nicin in beer, cheeses, sausages and dipping sauces) can also have significant impacts on the gut microbiome
• adverse effects of medications
  • antibiotics are a prime issue affecting the microbiome
  • long-term use of non-opioid analgesics has been found to alter the composition of gut microbiota and circulating levels of gut microbiota-derived metabolites
    • long term salicylic acid use was associated with a reduced abundance of eight microbiota traits, including genus Clostridium sensustricto, Adlercreutzia, Akkermansia, family Clostridiaceae, and Verrucomicrobiaceae, phylum Verrucomicrobia, class Verrucomicrobiae, and order Verrucomicrobiales and an increased abundance of the family Prevotellaceae. NSAID exhibited only one causal association with the increased abundance of group Eubacterium xylanophilum.⁷⁾
  • many other medications can affect the gut microbiome and promote pathogenic bacteria such as Salmonella typhimurium, and pathogenic gammaproteobacteria species are protected from many drugs by their selective outer membrane ⁸⁾

• the GIT microbiome consists of a wide range of bacteria, viruses, viroids, fungi, archaea and parasites which have complex interactions and effects
  • circular RNA viroid sequences in the shape of obelisks are found in roughly seven percent of human gut bacteria and 50 percent of mouth bacteria (esp. Streptococcus sanguinis). The gut-based structures also feature a distinctive RNA sequence when compared to the mouth-based viroid obelisks. ⁹⁾ They produced proteins called “oblins”.
  • unlike bacteria, archaea are a distinct domain of life with unique cellular and genetic features
    • Methanobrevibacter intestini produces methane from hydrogen and CO₂ as well as high levels of succinic acid—a compound linked to inflammatory processes
    • GRAZ-2 variant of Methanobrevibacter smithii produces formic acid, which may impact the metabolism of neighboring gut microbes ¹⁰⁾
• long-term diet is strongly associated with the gut microbiome composition
  • those who eat plenty of protein and animal fats have predominantly Bacteroides bacteria, while for those who consume more carbohydrates the Prevotella species dominate¹¹⁾
• human genetic variation also has a significant contribution to the microbiome
  • 2025 study found 148 fungi associated variants (FAVs) across 7 chromosomes that statistically associate with 9 fungal taxa and this may impact risks for diseases ¹²⁾
    • the relative abundance of gut yeast Kazachstania associates with genetic variation in CDH13 encoding T-cadherin, a protein linked to cardiovascular disease.
      • interestingly, Kazachstania was found in previous studies to be a key gut commensal in mice where it regulates innate immunity
    • they identified FAVs that both overlap with protein-coding genes and associate with tissue-specific gene expression (FAV-eQTLs), suggesting triadic interactions with human genetic background, gut fungi, and antifungal immunity. Notably, all gut fungi that statistically link to FAV-eQTLs are lineages with known human pathogens.
• various parts of the gut have region specific microbiomes:
  • stomach which is highly acidic:
    • was once thought to be sterile but now it has been realised the microbial load of the stomach is approximately 10²–10⁴ colony−forming units (CFU)/ml, which is much lower than that of the intestine (10¹⁰–10¹⁴ CFU/ml), gastric mucosa mainly consisting of Proteobacteria and Firmicutes while human gastric juice is mainly Firmicutes, Actinobacteria and Bacteroidetes
    • microbiome composition is affected by childbirth delivery mode (in infants), age, sex, ethnicity, diet, lifestyle, geography, use of antibiotics, use of proton pump inhibitors (PPIs) or histamine H2 receptor antagonists, and the presence of H. pylori
    • microorganisms most frequently isolated from the human stomach by culture-dependent methods were Veillonella, Lactobacillus, and Clostridium spp. ¹³⁾
    • bacteria present in the oral cavity and duodenum such as Veillonella, Lactobacillus, and Clostridium can transiently colonize the stomach
    • > 50% of population is infected with Helicobacter pylori usually from childhood, however, only a minority develop pathologic disease
      • most H. pylori strains can modulate the gastric environment, thus altering the habitat of resident microorganisms and increase risk of stomach cancer ¹⁴⁾
  • duodenum aerobic with rapid transits: the predominant phyla are Firmicutes and Actinobacteria
  • colon which is mainly anaerobic with slow transit times suited to fermentation: Bacteroides, Bifidobacterium, Streptococcus, Enterobacteriaceae, Enterococcus, Clostridium, Lactobacillus, and Ruminococcus
• use of proton pump inhibitors (PPIs), increase the gastric pH and modulate microbiota, influencing above all, Lactobacillus
• smokers tend to have higher levels of hydroquinone which allows Streptococcus mitus oral flora take residence in the gut which triggered the emergence of helper Th1 cells which fight against the Th2-immune response and this seems to be a mechanism for their reduced risk of ulcerative colitis ¹⁵⁾

• see also ageing
• opportunistic pathogens such as Enterobacteria, which can induce intestinal inflammation, increase, while by contrast beneficial commensals such as Bacteroides, Bifidobacteria and Lactobacilli decrease
• a genetic predisposition to higher levels of bacteria of the order of Coriobacteriales or of family Coriobacteriaceae increases the risk of developing AMD disease ¹⁶⁾

• Clostridia
  • spore-forming Gram-positive bacteria
  • Mitsuokella
    • a prevalent and efficient phytate degrader in the gut, converting it into short-chain fatty acids (SCFAs) ¹⁷⁾
• Bacillota - Gram positive bacilli
  • Bacillales
    • Bacillus sp
    • Staph sp
  • Lactobacillales
    • Lactobacilli
      • anaerobic, gram-positive bacteria that metabolise sugars into lactic acid
      • genomic studies suggest they make up 0.3% of the colonic bacteria and 6% of duodenal bacteria
      • most are beneficial (exceptions include Lactobacillus delbrueckii which can cause apoptosis and necrosis):
        • support in restoring the intestinal lining after excessive inflammation
        • can restore altered immune cell proportions, examples include:
          • “L. reuteri increases the concentration of Tregs in mesenteric lymph nodes and prevents expansion of DCs and recruitment of neutrophils”¹⁸⁾
          • “L. rhamnosus reduces the Th17/Treg ratio through the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway , … and can also induce mitochondrial pathway-dependent apoptosis of specific immune cells, particularly monocytes, without disturbing intestinal epithelial cells (IECs)” ¹⁹⁾
          • “Both L. rhamnosus and L. salivarius protect mice from trinitrobenzene sulfonic acid (TNBS)-induced colitis”²⁰⁾
          • “Many Lactobacillus strains downregulate the production of pro-inflammatory mediators, such as IL-6, IL-1β, and tumor necrosis factor-α (TNF-α) in the inflamed tissues of colitis mice” ²¹⁾
          • “L. rhamnosus secretes HM0539, a novel soluble protein that downregulates the expression of cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS). These factors inhibit the production of nitric oxide (NO) and prostaglandin E2 (PGE2), which are crucial inflammatory mediators in the GI tract” ²²⁾
          • “Lactobacillus interventions, particularly L. rhamnosus GG secreting p40, in combination with vitamin D, exhibit favorable results in IBD patients.”²³⁾
    • Streptococci
      • Str. faecalis

• Bacteroidota
  • non endospore-forming, Gram-negative bacilli
  • some can degrade starch, cellulose, xylans, and pectins
  • phylum Bacteroidota and some Proteobacteria have the unique ability to produce sphingolipids - sphingolipids, such as sphingosine-1-phosphate, are critical regulators of leukocyte migration through tissues
  • play an important role in protein metabolism by proteolytic activity assigned to the proteases linked to the cell
  • Bacteroides
    • obligate anaerobic
    • are normally mutualistic, making up the most substantial portion of the mammalian gastrointestinal microbiota
      • they participate in the regulation of the intestinal micro-environment
      • Bacteriodetes make up ~20% of the microbiome
    • play a fundamental role in processing of complex molecules to simpler ones in the host intestine
      • sugar derivatives from plant material in the gut can be potentially toxic, bacteroides such as B. thetaiotaomicron can ferment these to beneficial products²⁴⁾
      • some can utilize urea as a nitrogen source
    • they also benefit their host by:
      • excluding potential pathogens from colonizing the gut
      • removing side chains from bile acids, thus returning bile acids to the hepatic circulation
      • they may affect the lean or obese phenotype in humans ²⁵⁾
        • in addition, low abundance of B. uniformis found in the intestine of formula-fed infants were associated with a high risk of obesity ²⁶⁾
      • some produce acetate and propionate during sugar fermentation. Acetate can prevent the transport of toxins from the gut to the blood while propionate can prevent the formation of tumors in the human colon.²⁷⁾
      • have capsular polysaccharides (CPS), which are tightly regulated, dynamic, and firmly attached glycan to the cell surface of Bacteroides which can act as immunomodulatory molecules. CPS are amongst the most diverse organic molecules - the structural and physical properties of CPS determine its effect on host health.
        • B. fragilis capsular polysaccharide-A (PSA) is protective against colitis, encephalomyelitis, colorectal cancer, pulmonary inflammation, and asthma, while oral administration of B. thetaiotaomicron inhibited the development of allergic airway disease in mice by inhibiting activation of Tregs and inhibition of Th2 response without promoting a Th1 response, possibly by changing the circulating concentration SCFAs²⁸⁾
    • human faeces may contain 10¹⁰–10¹⁰ cells per gram
    • main sources of energy in the gut are complex host-derived and plant glycans but they can use simple sugars
    • are resistant to a wide variety of antibiotics such as β-lactams and aminoglycosides, and many species have acquired resistance to erythromycin and tetracycline while clindamycin resistance is increasing
    • they can cause disease such as:
      • CNS infections including meningitis and brain abscesses via penetrating the blood brain barrier through the olfactory and trigeminal cranial nerves
      • abscesses in the neck and lungs
      • can be associated with appendicitis
      • may be associated with adiposity, insulin resistance and dyslipidaemia as well as an inflammatory phenotype
    • low levels of Bacteroides in gut:
      • increased inflammatory bowel disease (IBD), Crohn's disease
        • B. fragilis suppresses intestinal inflammation and regulates intestinal homeostasis via the production of SCFAs
      • a 2021 study showed a 5.6-times higher risk of osteoporosis fractures in the low Bacteroides group of Japanese postmenopausal women ²⁹⁾
  • Prevotella
    • oral, vaginal, and gut microbiota (esp. if diet is mainly carbohydrates and fibre rather than protein and animal fats in which case Bacteroides will dominate)
    • a large genus with high species diversity and high genetic diversity across strains which makes it difficult to predict their function, which can vary across individuals
    • Prevotella copri is deficient in the ability to degrade host glycans and is more genetically equipped for plant glycan degradation
    • probably has a common ancestor with Bacteroides but now appears to be antagonistic
    • made up 53% of the gut bacteria in West African children but were absent in age-matched European children ³⁰⁾
    • may result in infections such as:
      • aspiration associated: aspiration pneumonia, lung abscess, pulmonary empyema
      • oral-related infections (esp. haemin-requiring P. intermedia and P. nigrescens along with the asaccharolytic Porphyromonas gingivalis):
        • abscesses and burns in the vicinity of the mouth, bites, paronychia
        • chronic otitis media and sinusitis
        • periodontal disease and periodontal abscesses including pregnancy gingivitis and acute necrotizing ulcerative gingivitis
      • bacteraemia seeding infections following URTIs - brain abscesses, osteomyelitis
        • overgrowth of Prevotella and a reduction of Lactobacillus correlated with the onset of osteomyelitis in mice while reduction of Prevotella in model mice led to an increase of Lactobacillus resulting in a protection effect against osteomyelitis.
      • bacterial vaginosis
        • Prevotella is the most heritable bacterial group in vaginal microbiome and its abundance is linked to body mass index and hormonal milieu
        • overgrowth at the expense of Lactobacilli results in bacterial vaginosis
          • Prevotella bivia produces lipopolysaccharides and ammonia that are part of vaginal mucus, is associated with epithelial cytokine production and enhances the growth of other bacterial vaginosis-associated organisms, such as Gardnerella vaginalis which in turn stimulates the growth of Prevotella bivia
      • urinary tract infection
    • increased levels of Prevotella copri:
      • may be associated with rheumatoid arthritis
      • may contribute to chronic inflammation in HIV patients
    • much less resistant to antibiotics than Bacteroides - 70% to penicillin, 30% to clindamycin, < 10% resistant to amoxicillin/clavulanate and metronidazole

• a diverse phylum of Gram-positive bacteria with high G+C content
• Bifidobacterium
  • the most common bacteria in the microbiome of human infants
  • help maintain the mucosal barrier and reduce lipopolysaccharide in the intestine
  • confer myriad health benefits which have a role in anti-infection, anti-cancer, anti-inflammation, anti-obesity, and others ³¹⁾
• Gardnerella
• Streptomyces

• Proteobacteria
  • Gram negative bacilli
    • E.coli
      • colibactin-producing E.coli strains which may become part of the microbiome in childhood may contribute to risk of early onset colorectal cancer (bowel cancer) as these cancers have over 3x the rate of colibactin-induced mutations
        • it is thought that modern lifestyles such as antibiotics, processed foods, reduced breastfeeding, C-sections, and group childcare may contribute to risk of these organisms being in the microbiome
• Cyanobacteria
• Fusobacteria (not good!)
  • these appear to become prominent in those with diets high in taurine (eg. energy drinks), high sugar, low fibre diets and are thought to increase inflammation throughout the gut by binding to pro-inflammatory proteins and thereby increasing cell aging and risk of colorectal cancer (bowel cancer)
• Verrucomicrobia

• archaea
• bacteriophages
• eukaryotic viruses
• fungi
• gut parasites
  • Blastocystis
    • Blastocystis carriage was linked to healthier diets and favorable cardiometabolic profiles, with higher prevalence in those consuming plant-based, minimally processed foods. ST4 was common in Westernized regions but rare in Asia and absent in South America and Africa. ST1 and ST2 were more prevalent in non-Westernized populations.³²⁾

• Bacteroides
  • Bacteroides is a major and predominant genus of gut bacteria where both the host and bacteria benefit from a mutualistic relationship
  • Bacteroides spp. provide nutrition, amino acids, vitamins, and short-chain fatty acids (SCFAs) to the host and supports other resident intestinal microbiota
  • Bacteroides species play a role in the stimulation, development, and homeostasis of the immune system and the prevention of bacterial and viral infections
  • Bacteroides spp. are generally beneficial and sometimes harmful within the gastrointestinal tract and are primarily pathogenic in extraintestinal locations. ³³⁾
    • appear to be linked to severity of malarial infections (see below)
• malaria severity
  • plasmodium infections have been shown in murine malaria to change gut bacteria
  • in 2023, mice studies and human studies on Ugandan children appear to show a causal relationship between a consortium of microbiome with critical involvement of certain Bacteroides sp. (esp. B. caccae ) in gut microbiome and increased severity of malarial infection. ³⁴⁾
    • They authors suggest possible mechanisms:
      • gut microbiota composition impacts the severity of malaria via dynamic modulation of spleen germinal center reactions
      • gut bacteria modulation of heme metabolism as the number of genes belonging to KEGG modules alpha-Hemolysin/cyclolysin transport system was >2.5 log2FC (fold change) in susceptible mice compared to resistant mice.
      • Stap. aureus producing alpha haemolysins are exotoxins which result in haemolysis and generation of harmful metabolites like labile heme which are required by Plasmodium parasite as a metabolic cofactor.
      • Bacteroides supports maintenance of this gut consortium
• relationship with serum uric acid levels and gout:
  • Gut microbiota taxa has a key influence on SUA levels and the development of gout and the microbiome composition is influenced by gout and SUA levels ³⁵⁾
• Alzheimer's disease
  • Nutrients 2023, 15(21), 4661 Lipids, Gut Microbiota, and the Complex Relationship with Alzheimer’s Disease: A Narrative Review
• materno-fetal implications
  • Microbiota–host interactions during pregnancy are key for maternal and neonatal health outcomes and healthy offspring development ³⁶⁾
• effects of nicotine
  • Keto B as a regulator of body weight loss associated with nicotine administration ³⁷⁾
• recurrent UTIs
  • a small study suggests reduced diversity of gut microbiome appears to be associated with recurrent UTIs ³⁸⁾
• urolithiasis / renal stones / renal calculi
  • the removal of probiotics represented by lactic acid bacteria and the colonization of pathogenic bacteria can directly or indirectly promote the occurrence of kidney stones.
  • oxalate-degrading bacteria, such as Oxalobacter formigenes, which require a strictly anaerobic environment to survive, tend to colonise in the colon however, much of the oxalate is absorbed in the proximal parts of the intestine before it gets to this organism ³⁹⁾
• multiple sclerosis (MS)
  • a 2025 study suggests Eisenbergiella tayi and Lachnoclostridium in the gut microbiome may trigger MS ⁴⁰⁾