Oral and Gut Microbiota Changes During Long-term Fasting in Humans

Healthy Clinical Trial

— OralFast  

Official title:

Oral and Gut Microbiota Changes During Long-term Fasting in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05449249
• Other study ID #: BuWi_OralFast_2022
• Status: Completed
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: January 6, 2023

Study information

• Verified date: January 2023
• Source: Buchinger Wilhelmi Development & Holding GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this longitudinal trial is to investigate the effects of a 10±3-day fasting period in 30 subjects. Changes in the oral and gut microbiota, halitosis, as well as inflammatory and antioxidative parameters and biomarkers of sulfur metabolism will be analysed.

Description:

Fasting has been linked with changes in gut microbiota as part of the physiological adaptation. Furthermore, associations have been described between oral disease and nutrition (diet rich in carbohydrates). The aim of the present longitudinal clinical study is to explore the effect of a 10±3-day fasting period on the oral and gut microbiota. 30 systemically healthy subjects attending the Buchinger Wilhelmi Clinics for fasting, will participate. Changes in oral microbiota will be assessed in plaque and saliva samples and a number of inflammatory markers will be analyzed in Gingival Crevicular fluid (GCF) and blood obtained before, during and after the fasting period. The changes in the oral microbiota will be associated to the composition of the gut microbiota. Changes in periodontal parameters and halitosis related to the fasting period will be further evaluated. Given the known association between sulfur metabolism and the redox status, parameters from the antioxidant status and oxidative damages will also be assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 6, 2023
• Est. primary completion date: October 8, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Both subjects with periodontitis and healthy periodontium will be included.

• Signed informed consent

Exclusion Criteria:

• Not able to sign the informed consent

• diagnosticated with cachexia, anorexia, nervosa, advanced kidney, liver or cerebrovascular insufficiency

• Smoking

• the intake of antibiotics within the last 8 weeks, as well as the intake of probiotics within the last 4 weeks

• periodontal treatment in the last 6 months

• chronic manifest psychical and psychiatric diseases

• participation in another study

• pregnancy or breastfeeding

Related Conditions & MeSH terms

• Healthy
• Periodontitis

Intervention

Procedure:
• Long-term fasting
The participants will undergo a fasting program that includes the daily intake of 250 kcal under medical supervision.

Locations

Country	Name	City	State
Germany	Buchinger Wilhelmi clinic	Überlingen

Sponsors (5)

Lead Sponsor	Collaborator
Buchinger Wilhelmi Development & Holding GmbH	Buchinger Wilhelmi Clinic, ETH Zurich (Switzerland), King's College London, University of Geneva, Switzerland

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in Rosenberg scale	organoleptic intensity scale for measuring oral malodor: 0 = no odor to 5 = intense odor	daily from baseline to the 3rd day of food reintroduction
Other	Changes in Seemann scale	organoleptic assessment: 1 = odor noticable from 10 cm to 3 = odor noticeable from 1m	daily from baseline to the 3rd day of food reintroduction
Other	Changes in Ayurvedic diagnosis of the tongue	examination of the tongue	daily from baseline to the 3rd day of food reintroduction
Other	Changes in urinary ketone bodies	using ketostix	daily from baseline to the 3rd day of food reintroduction
Other	Changes in capillary blood ketones	using GlucoMen areo 2k	daily from baseline to the 3rd day of food reintroduction
Other	Changes in capillary blood glucose	using GlucoMen areo 2k	daily from baseline to the 3rd day of food reintroduction
Other	Changes in ph value of the urin	using test strips	daily from baseline to the 3rd day of food reintroduction
Other	Changes in weight	kg	daily from baseline to the 3rd day of food reintroduction as well as 1 and 3 months after
Other	Changes in blood pressure	systolic and diastolic in mmHg	daily from baseline to the 3rd day of food reintroduction as well as 1 and 3 months after
Other	Changes in pulse	beats per minute	daily from baseline to the 3rd day of food reintroduction as well as 1 and 3 months after
Other	Plaque Index score	Sillness & Loe, 1964: from 0 = no plaque to 3 = abundant plaque along the gingival margin, interdental spaces filled with plaque	baseline
Other	Gingival index score	Löe & Sillness, 1963: from 0 = normal gingiva to 3 = severe inflammation	baseline
Other	Probing pocket depth	Bleeding on probing, recorded as present within 30 sec (1) or absent (0)	baseline
Other	clinical attachment level	distance between the cemento-enamel junction and the tip of the graduated steel	baseline
Other	recession	distance between CEJ and marginal edge of the free gingiva	baseline
Other	Changes in leucocytes	(thousands/µl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in erythrocytes	(millions/µl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in haemoglobin	(g/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in haematocrit	(in %)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in MCV	(fl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in MCH	(pg)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in MCHC	(g/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in thrombocytes	(thousands/µl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in international normalized ratio	ratio	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in Quick	(in %)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in partial thromboplastin time	(sec)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in aspartate aminotransferase (AST/GOT)	(U/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in alanine aminotransferase (ALT/GPT)	(U/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in gamma-glutamyl transferase (GGT)	(U/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in alkaline phosphatase	(U/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in uric acid	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in urea	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in glomerular Filtration Rate (GFR)	(ml/min/1.73m2KOF)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in creatinine	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in thyroid-stimulating hormone (TSH)	(mE/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in total cholesterol	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in triglyceride	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in high-density lipoprotein (HDL)	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in low-density lipoprotein (LDL)	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in LDL / HDL - ratio	ratio	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in glucose	(mg/dl)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in HbA1c	(mmol/mol)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in sodium	(mmol/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in potassium	(mmol/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in calcium	(mmol/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in magnesium	(mmol/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in erythrocyte sedimentation rate	(mm/h)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in C - reactive protein	(mg/l)	Baseline, fasting day 10, and food reintroduction day 3
Other	Changes in pH value of saliva	(mol/l)	Baseline, fasting day 10, food reintroduction day 3, 1 and 3 months afterwards
Primary	Changes in halitosis	Concentration of volatile sulfide compounds (hydrogen sulfide, methylmercaptan and dimethyl sulphide) using the OralChrome devise	daily from baseline to the 3rd day of food reintroduction
Primary	Changes in microbiota compositions of subgingival microbial and plaque sampling	Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Parvimonas micra (Pm) and Prevotella intermedia (Pi) analysed by RT-q-PCR	Baseline, fasting day 10, food reintroduction day 3
Primary	Changes in microbiota composition in saliva	16 rRNA gene amplicon sequencing	Baseline, fasting day 10, food reintroduction day 3, 1 and 3 months afterwards
Primary	Changes in microbiota composition in faeces	16 rRNA gene amplicon sequencing	Baseline, first spontaneous stool after food reintroduction (up to day 3), 1 and 3 months afterwards
Primary	Changes in total antioxidant capacity (TAC)	(mmol DPPH/L)	Baseline, fasting day 3, 5, 10
Primary	Changes in hydrogen sulfide production capacity	measured in serum and urine using the lead acetate assay	at the beginning and the end of fasting, on day 3 and 5, as well as at the food reintroduction
Secondary	Changes in glutathione (GSH)	(µmol/g Hb)	Baseline, fasting day 3, 5, 10
Secondary	Changes in thiobarbituric acid reactive substances (TBARS)	(µmol/L)	Baseline, fasting day 3, 5, 10
Secondary	Changes in malondialdehyde (MDA)	nM/L	Baseline, fasting day 3, 5, 10
Secondary	Changes in protein carbonyls	(nmol/mg protein)	Baseline, fasting day 3, 5, 10
Secondary	Changes in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase	(µL)	Baseline, fasting day 3, 5, 10
Secondary	Changes in glutathione reductase (GR) activity	(U/g Hb)	Baseline, fasting day 3, 5, 10
Secondary	Changes in glutathione peroxidase (GPx) activity	(U/g Hb)	Baseline, fasting day 3, 5, 10
Secondary	Changes in peroxiredoxin activity	(U/g Hb)	Baseline, fasting day 3, 5, 10
Secondary	Changes in catalase (CAT) activity	(U/mg Hb)	Baseline, fasting day 3, 5, 10
Secondary	Changes in superoxide dismutase (SOD) activity	(U/g Hb)	Baseline, fasting day 3, 5, 10
Secondary	Changes in hydroxyl radical scavenging	(mmol deoxyribose/ml)	Baseline, fasting day 3, 5, 10
Secondary	Changes in superoxydradical scavenging	(mmol NBT/L plasma)	Baseline, fasting day 3, 5, 10
Secondary	Changes in ABTS scavenging	(mmol/L)	Baseline, fasting day 3, 5, 10
Secondary	Changes in reducing power	(mmol/L plasma)	Baseline, fasting day 3, 5, 10
Secondary	Changes in thiosulfate	measured using the monobromobimane method using HPLC and LC-MS/MS	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in persulfidation	persulfidation in serum and urine	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in cystein	using the S-sulfocysteine (SSC) method which is a HPLC-based method using automated precolumn derivatization with OPA and UV detection at 338 nm in serum and urine	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in amino acid metabolites	using a targeted approach in serum and urine	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-10 in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in G-CSF in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IFN-? in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in TNF-a in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-1ß in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-6 in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-8 in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-17 in blood	analysed in blood with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-10 in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in G-CSF in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IFN-? in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in TNF-a in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-1ß in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-6 in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-8 in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3
Secondary	Changes in IL-17 in gingival crevicular fluid	analysed in gingival crevicular fluid with Bio-Plex 200 Suspension array System	Baseline, fasting day 10, food reintroduction day 3