Gut-Skin access

Microbiome: seeded from birth: the first microbial communities train the immune system to
tolerate commensal organisms while remaining alert to pathogenic strains. May factors
influence over time.

Varied benefits:

Dysbiosis: reduced beneficial strains, over proliferation of pathogenic strains or reduced

overall microbiota variety.

Skin:
- Largest organ in the body
- Skin protects the internal organs, regulates temporal control and communicates with
the immune system.
- Skin microbiome: a unique collection of micro-organisms exists on the skin. Different
to gut microorganisms as subjected to a harsher environment.
- Impacted by UV, injury, salty, dry, acidic and nutrient poor. : mainly lipid and base
proteins rather than carbohydrates.
- Different parts of the skin have different microbiomes.
- 1000 bacterial species mainly within the genera: Brevibacterium, Micrococcus,
Staphylococcus, Streptoccus etc.
- Dermatological disorders:
Acquired or temporary conditions such as atopic dermitis, psoriasis, acne, rosacea.
Congenital inherited conditions e.g. EB, Ichtyosis, Nethertons Syndrome.
- GI symptoms in EB: reduced intake, oral mucosa damange, mcirostoma, blistered
gums, high losses from skin e.g fluid, plastma, electrolytes, high nutritional
requirements, gastro mucosal involvement.
- Gut-Skin axis: Bidirectional relationship e..g Vit D, allergens with skin, whereas gut on
skin: dermatological conditions e.g. in d coeliac.
- Skin Microbiome: lots of chemicals produced, differentiates between commensal
bacterial and harmful strains. Produces anti-inflammatory chemicals , protect the
structure of the skin: chemicals that tighten the epithelial tight junctions. Involved in
wound healing.
- Antibiotics in dermatology: may change the composition and function of our
microbiomes, killing on inhibiting growth. Oral administration of vancomycin for the
treatment of infected skin wounds. Reduced bacterial diversity and regenerate gene
gemma expression.
- Burns: a good example to look at the skin microbiome. : during an acute/severe
burn: dysbiosis occurs. Can predict the timeline and how this impacts the patient.
- Not clear if dysbiosis causes the dermatological disorder or vice versa. Emerging
body of evidence on the use of probiotics in the treatment of these conditions.
- More severe psoriasis = more significant change.
- Probiotics: reduced CRP, increase butyrate.
- RDEB children: significantly reduced alpha diversity compared with that of healthy
controls. Significantly early age-dependent predominance of staph aureus, first in
wounded skin and then in unwounded skin.
 - Small study by author: multi-strain probiotic substantial improvement in symptoms
including pain, abdo pain, flatulence and increase in appetite.
- Is moving to case-controlled study.
- Atopic dermatitis/Ecsma: Prevention evidence : studies have shown spikes in staff
aureus, studies have show potential benefits of probiotics: e.g. Lactobacillus
rhaminosus GG.
- Dysbiosis in infancy linked to development.
- Mixed results: no conclusive evidence to use probiotics in the treatment of eczema:
Lactobacillus rhamnosus, Bifidobacterium lactis – more evidence needed.
- American Academy of allergy and immunology: doesn’t recommend. Cochrane 2022:
may not be evidenced based. WHO: suggests using probiotics.
- Prevention
- BSACI guidelines: introduce allergens early in weaning. All foods are safe until an
allergic reaction is proven. Allergen testing best done when skin is well controlled
with topical regimens otherwise can show false positives. Allergy testing
interpreteded by experienced clinicans.
- ISAPP/WGO Practice Guidelines (2022): up to date collection on data on different
conditions. Practice Guidelines (2023) – safety of probiotics and prebiotic
supplements is paramount. Live cultures not recommended for
immunocompromised, pancreatitis, ICU, melaena, central veanus catheter.
- Med diet/ Medetasian – evidence mixed with skin. Good evidence in psoriasis and
acne, but not eczema.

Faecal microbiota transplants: how it works and why it doesn’t: Dr James Kinross (surgical
specialty).
- Gut microbiome is massive, highly variable, incomplete.
- Gut Phage Database: huge, we don’t know a lot of what is really there and not
enough data.
- Many unknowns remain: do we need the whole microbiome? When is the optimum
time for dosing? What is the optimum role? What do we feed these? Can this be
targeted in individuals?
- STRAIN specific functions important: Aravacteroids goldsteninii exerts and local anti-
inflammatory effect on the anastomosis.
- The age of microbiome therapeutics: Level 1a Diet, pre/pro/syn/post biotics –
Vaccines., phage therapy, FMT and synthetic biology.
- Chinese practioners used it for travels diarrhoea in very early years. 283-343 CE.
- C.Diff: Abx resistant C.diff: patients given in FMT had such a high level of cure it was
paused early as felt it was unethical to continue abx.
- Since then wealth of evidence on C.diff and FMT.
- FMT in practise: donated or own faeces, diluted mixed and filtered, transplanted in
usual faecal microbiota transplantation. (55% will be microbiota and the rest soluble
components such as mucus, proteins, fats, small molecules such as bile acid and
SCFA – these are not well understood).
- Given by e.g nasogastric tube and bowel lavage. – Highly regulated interventions –
requires MHRA approval.
- Problem with a lot of FMT process as aerobic so organisms die. Anaerobic prep is
being used.
- Future - ?trying to industrialise that process. Donation is a problem and to increase
scale.
- In early stages of commercial development.
- FMT known in media: side effects such as hair growth. – triggered RCTs.
- High and low quality trials.
- FMT in Europe: United Kingdom does the most.
- NICE approval for C.diff.
- Interest in IBS, UC etc but in small numbers.
- How does it work? We don’t fully know – challenging to unpick. Bioremediation
(removal of toxins), restoration of diversity, ecological remodeling, metabolic
function, EEC function, hormone bioavailability, gut barrier, immune modulation and
ENS interactions.
- ?species might have increased chance to grow when pre-existing climax species are
eliminated.
- FMT: modifies bile salt hydrolases: imperial study on c.diff treatment. – FMT seems
to mediate c.diff through modification of bile salt hydrolases.
- ‘Superdonor’, fantasy or reality?: observation in early trials that some doners are
more effective than others – can identify them?. In norway they identified 14 out of
39. However, without understanding the mechanism we can't conclude it. May not
make an impact on bigger scale, may not be the bacteria that causes it.
- ?could it be the recipient. Aiming for coexistence of donor and recipient strains.
- NICE: now recommended for recurrent c.diff in 2 or more previous confirmed
episodes. Also cost effective. Access poor.
- Guidelines and consensus: for IBD: evidence and cautious.
- Ulcerative Colitis: causes shifts in the gut microbiome. NR or Relapse non-reponders
- Very significant heterogenomity in the studies: only 1 anaerobic studies. Some give
antibiotics some don’t, some follow up at 12 weeks, some not.
- Before even determining the outcome measures: different to make a summary or
statement.
- UC: clinical and endoscopic benefit in the short term treatment: fairly safe.
Chochrane have just released their review: may increase the proption of people with
active UC.
- Crohns: moderate evidence.
- IBS dataset: route of administration is important.
- Metanalysis: high dose FMT by NG tube (60g) effect improved – as small bowel
disease driving it.
- 2021 trial: metastatic melanoma: resistant to drug that is so effective. FMT used to
see if it improves: were able to identify the types of microbes. Means you can
engineer the gene microbiome environment in advanced ca care.
- FMT challenges: feeding FMT after an intervention is AS IMPORTANT as the
intervention itself. – requires dietitian and nutritional strategy.
- FMT in obesity: Harvard. Insulin resistance – fibre supplementation impacted results
and overall diabetes profile.
- ‘Anti-inflammatory diet’ and FMT and UC: could sustain remission until 1 year and
was more effective than standard medical therapy alone. When diet is controlled,
remission is much more likely to occur. Was more successful than steroid
intervention. FEEDING AFTER is important.
- FVT: faecal virome transplant: ultrafiltrating your faecal specimen: small studies atm.
- C.diff: doner derived. Something in the virome alters FMT response. – not all about
bacteria, also virus’ but mechanism is not fully understood.
- Ways fungi is important in mucosal and barrial health.
- Not all about the gut. Vaginal microbiota starting to be trialled: women who suffer
from infertility. Single case report of pt with recurrent miscarriages. Lactobacillus
was depleted: first FMT changes composition. Then remained stable and carried
baby to full term.
- Safety: gut microbiome is so infuencial that we don’t know how we are altering
immune function, cancer risk and other conditions. For metastatic conditions less of
a worry but e.g. for IBS more worrying risk. Long term risks unknown.
- Should we actually be calling it intestinal microbiota transplant?
- Matching doner: what is a good doner? – most profiles will recruit for similar
phenotypes with no history of chronic diseases including metabolic conditions.
- Cecerean – swabbed and put on babies face: understanding how infants born by c-
section immune system may be improved. Controversial, lots of confounders.
- Paediatric Crohns disease there is an increased growth.
- Bug-lipid interactions and risk of inflammation.
- Misuse of antibiotics.
- Has a book on this.