Malabsorption and Gut Microbiota Profile Changes After Laparoscopic Mini-Gastric Bypass (MGB) vs Roux-en-Y Gastric Bypass (RYGB): a Prospective Multicenter Comparative Study
Phase: NA
Conditions: Obesity (Disorder)
Sponsor: University of Roma La Sapienza

 
 
MALABSORPTION AND GUT MICROBIOTA 
PROFILE CHANGES AFTER LAPAROSCOPIC 
MINI-GASTRIC BYPASS VS ROUX-EN-Y 
GASTRIC BYPASS:                                          
A PROSPECTIVE MULTICENTER 
COMPARATIVE STUDY 
 
23/01/2018 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
RESEARCH UNITS 
1. Principal  Investigator  :  Prof.  Gianfranco  Silecchia  M.D.  PhD,  
Director Division General Surgery & Bariatric Center of 
Excellence-Centro di Ecellenza Sicob.  – “Sapienza” University 
of Rome – Polo pontino – gianfranco.silecchia@uniroma1.it 
Research  fellows:  Cristian  Boru,  (MD  PhD  student),  Angelo 
Iossa  (MD  PhD  student),  Marcello Avallone  (MD  Resident 
general surgery), Emanuela Paone (psycholgist) 

2. Metabolic  and  Obesity  Unit  “Sapienza”  University  of  Rome  - 
Policlinico Umberto  I, Rome, Italy:  Frida  Leonetti  (Associated 
professor of endocrinology), 
Danila 
Capoccia 
(Clinical 
Research  Fellow,  endocrinologist),  Federica  Coccia  (Research 
Fellow,endocrinologist) 
3. Stefano 
Ginanni 
Corradini 
MD 
PhD: 
Professor 
of 
Gastroenterology,  Department  of  Clinical  Medicine,  Sapienza 
University of Rome, Rome, Italy. 
4. Mario  Musella  MD:  General  Surgery  Professor,  “Federico  II” 
University of Naples, Department of Medico-Surgical Sciences 
and  Biotechnologies,  AOU  "Federico  II",  Naples,  Italy.  Co-
workers: Brunella Capaldo MD (Associated Professor of 
Endocrinology), Paolo Bianco MD (Resident General Surgery) 
5. Miguel Ángel Carbajo MD PhD: Director of Centre of 
Excellence for the study and Treatment of Obesity and Diabetes, 
Valladolid, Spain. 
6. Fredrik Bäckhed MD PhD: Departments of Molecular and 
Clinical  Medicine  (the  Wallenberg  Laboratory),  University  of 
Gothenburg, Gothenburg, Sweden. 

7. Antonio  Molinaro  MD  PhD:  Departments  of  Molecular  and 
Clinical  Medicine  (the  Wallenberg  Laboratory),  University  of 
Gothenburg, Gothenburg, Sweden. 
Background: 
Bariatric surgery is the best choice to treat morbid obesity and its severe 
co-morbidities (1, 2, 3).In 1997, Robert Rutledge proposed a new procedure, the 
mini gastric bypass (MGB), a variation of the Roux-en-Y gastric bypass 
(RYGB) with a single anastomosis (3). MGB seems to provide similar results as 
concern  weight  loss  and  control  of  metabolic  co-morbidities  while  presenting 
the  benefit  of  being more  easily  laparoscopic  performed  and  revisable  (4, 
5).However,  this  operation  is  still  controversial  because  of  biliary  reflux  and 
possibly increasing the risk of esophageal cancer in absence of  validated steps 
of the procedure (volume of the gastric pouch, type  gastro-jejunal anastomosis, 
distance from Treitz) (6).  
The biliopancreatic limb length may explain the results of superior excess 
weight reduction as well as the higher incidence of hemoglobin deficiency after 
5  year  follow-up  comparing  MGB  vs  RYGB  (7).  This  malabsorption  could 
results in severe malnutrition defined as a %EBMIL > 100 % and an albumin 
level < 30 g/l (8). 
In 2005 Rutledge observe  malnutrition in 31/2,401 patients (5), Noun et 
al. reported 4 casesof malnutrition out of 1,000 patients of MGB (9), Lee et al. 

(10) reported a revision rate of 1.7% at 9 years follow-up in their series of 1,322 
patients andthemost common cause of revision was malnutrition in nine cases. 
In addition, Wang et al. (11) operated 423 MGB and reported anemia as a late 
complication in 28% of patients, and most cases were microcytic, the reason for 
the  high  incidence  was  reported  to  be  likely  due  to  the  duodenal  bypass  with 
malabsorption of iron. However all data published on the mal-absorptive effects 
of  MGB  are  retrospective  so,  until  now,  there  is  no  prospective  comparative 
study  to  assess  the  malaborbitive  efficacy  of  MGB  vs  RYGB.  Recently  an 
experimental  study  carried  out  in  a  rat  model  evaluated  the  malabsorption  of 
MGB    versus  RYGB  suggesting  a  higher  protein  malabsorption  induced  by 
MGB (not compensated by the intestinal adaptation) then RYGB (12). 
Recent works have indicated that the gut microbiota may mediate some of the 
beneficial  effects  of  bariatric  surgery,  and  changes  in  the  composition  and 
diversity of the gut  microbiota  have been  observed  in the short and  long  term 
after RYGB in humans (13, 14), as well as after vertical sleeve gastrectomy and 
RYGB  in  mice  (15).  However,  there  are  no  investigations  of  these  changes  
after MGB. 
AIM OF WORK: 
To evaluate in patient undergoing MGB or RYGB the effect of the treatment on 
enteric mal-absorption and microbiota profile in the first year after  surgery. 
Primary end point: 

-To  evaluate  and  compare  RYGB  vs  MGB  bile  acids  levels  and  microbiota 
profile shift at 6 and 12  months after surgery and its impact on metabolic and 
nutritional status after surgery.  
Secondary end point:  
-To measure GLP-1 plasma level (pg/mL) before and 12 months after surgery in 
MGB vs RYGB patients. 
 
Other parameters: 
1. To evaluate at 0 – 6 and 12 months after surgery the enteric mal-absorption 
profile  in  terms  of  lipid  (Triglycerides,  cholesterol,  HDL  and  LDL),  proteins 
(hemoglobin, albumin and ferritin), carbohydrates and micronutrients (minerals 
and vitamins) and nutritional status in subjects undergoing MGB vs RYGB. 
2.  To  compare  the  effect  of  RYGB  vs  MGB  surgery  on  total  weight  loss 
percent,  excess  weight  loss  percent  (%EWL),  excess  BMI  loss  percent,  major 
co-morbidities control and quality of life. 
3. To evaluate the endoscopic /histological esophageal mucosal lesions 
secondary to bile reflux at 12 months in MGB vs RYGB patients 
4. to evaluate energy expenditure at 0 and 12 months by Indirect calorimetry 
 

Type of study: 
Multicentric Prospective pilot comparative study. 
 
Patients: 
We had to evaluate Sample Size using bariatric patients population who 
underwent  MGB  or  RYGB  during  12  months  (the  follow  up  period  of  this 
study) in the three centres involved in the study, because of there aren’t others 
high methodological level studies or randomized trials or methnalysis about this 
argument (Primary end points and secondary and points). Our population is 285 
patients: to obtain a confidence level of 95 %, an effect size of 0.5, Sample size 
is 90 patients (45 MGB and 45 RYGB) with an interval confidence of 8.56. 

Tab 1 
Tab 2 
The sample size will be 90 cases (45 MGB and 45 RYGB) considering at least 
20% drop-out at 1 year. (Tab 1-2) 
 
 
 
Inclusion Criteria: 
Obese patients with age 18-65 years old, BMI 40-55 kg/m
2, non smokers, and 
candidates to primary MGB or RYGB without any concomitant surgeries except 

hiatal  hernia  repair.  Patients  will  be  informed  on  the  differences  of  the  two 
procedures and the enrollment in the two study groups will be on the basis of 
patient choice. 
Exclusion Criteria: 
 Age ≤ 18 or ≥ 65 years old,  
 BMI≤ 40 or ≥55 
 Smokers 
 Any required associated surgical procedure except hiatal hernia repair 
 Conversion to open surgery 
 Postoperative complications requiring reoperation 
 No compliance to the follow up schedule.  
 Histological positivity to Helicobacter pylori previous or current  
 Patients  with  different  intraoperative  measurement  of  the  bowel  distal  to 
Treitz Ligament (tolerance plus or minus 10%). 
 Free PPI 4 weeks  before 6th month (after surgery) 
 Corticosteroids, vitamin E, fish oil treatment in the previous two months  
 Anti or pre- biotics treatment in the previous 2 months  
 Chronic gastrointestinal diseases or syndromes (e.g., IBD, IBS)  
 Previous bariatric surgery (intragastric balloon excluded).  
 Previous resective bowel surgery 

 Previous pancreatic surgery 
 Previous hepato bilio pancreatic surgery 
 Gallbladder gallstones 
 
 
 
 
Methods: 
Pre-and post-operative Assessment: 
All  patients  will  sign  an  informed  consent  (Sicob  guidelines  2016).  Study 
protocol will be approved by the Ethical Committee.  
All patients will undergo routine blood laboratory investigations before surgery, 
6  months  and  12  months  after  surgery  including:  serum  hemoglobin,  glucose, 
HbA1c, cholesterol, triglycerides, LDL, HDL, T3, T4, TSH, GLP-1. 
Assessment of the nutritional status will be performed before 6- and 12 months 
after  bariatric  surgery  by  blood  testing for  serum iron,  calcium,  zinc  and 
vitamins A, D, B12 and cortisol level. 
A  standardized  meal  test  will  be  performed  before,  6  and  12  months  after 
bariatric surgery with 250 ml of liquid meal Oxepa®, (375 calories, 55.5% fat, 

28% carbohydrate, 16.5% protein). Blood samples will be collected at baseline, 
30, 60, 90 and 120 minutes after meal test in order to assess the concentration of 
the circulating lipids, GLP-1, bile acids (C4 precursor of bile acids) and FGF 19 
(Fibroblast Growth Factor 19) levels. A stool sample will be collected at 0 – 6 – 
12  months  (It’ s  necessary to  indicate date and  time  of defecation) stored at  -
80°C for targeted gut microbiota metagenomic (MG) study, lipids and proteins 
levels assessment. Every sample will be made by two parts: one for 
metagenomics evaluation and the other one for lipids and proteins levels 
assessment.      Before  fecal  sampling,  patients  will  be  asked  to  fill  out  a  three 
days  food diary.  All patients with  vitamin D deficiency (< 20  ng/mL) will be 
supplemented  before  surgery  with  10,000  IU  of  Vitamin  D
3  daily  (16).  Every 
value of nutritional status shoud be annotated in Winfood software. The 
selection criteria, work up, informed consent and schedule of the 
multidisciplinary  follow  up  will  follow  the  Guidelines  of  Italian  Society  for 
Obesity Surgery (SICOB) adopted in September 2016 (www.sicob.org). 
 
Intra-operatively: 
Standardization of the techniques will be guaranteed: 
1. RYGB group 
2. MGB group 

All patients will have intraoperative measurement of the whole length of 
bowel from Treitz ligament to the ileocecal junction (expected range 6-8 
m).The  common  limb  will  be  therefore  about  2/3  of  total  small  bowel 
length. 
 
Roux en Y gastric bypass 
The steps of the standard double loop RYGB technique will be followed (17). 
The gastric pouch will be created 7 cm from the gastro-esophageal junction to 
obtain a volume of 30-40 ml, and the length of the alimentary limb will be 150 
cm  and  3.5-4  cm  gastro-jejunostomy  will  be  performed  by  linear  stapler.  The 
length of the biliopancreatic limb will be from 65 to 75 cm beyond the ligament 
of Treitz. The lengths of both limbs should carefully measured with a graduated 
instrument. The mesenteric defects will be closed. 
 
Mini-gastric Bypass 
The  gastric  pouch  will  be  performed  starting  below  the  incisura  angularis 
(transverse resection 4 cm) on the lesser curvature (18).Then the stomach will 
be transected against a 36 Fr bougie up to the gastro-esophageal junction Then 
1/3 of the small bowel will be excluded (approximately 200cms) and 3.5-4 cm 
gastro-jejunostomy will be performed by linear stapler. 

Postoperative diet 
After surgery and under the supervision of the registered dietitian, the diet will 
be transitioned  from  liquid diet  for 2 weeks to pureed  proteic  diet  for 1 week 
then  soft  solid  proteic  diet  for  2  weeks  then  maintenance  (regular  food).  All 
patients  should  have  daily  vitamin  and  mineral  supplementation  up  one  year 
after surgery following the chart below: 
 
Vitamin A                                                    0,8 mg 
Vitamin B                                                    11,65 mg 
Vitamin B                                                    22,1 mg 
Vitamin B                                                    324 mg 
Vitamin B                                                    62,1 mg 
Vitamin B12                                                0,00375 mg 
Vitamin C                                                    120 mg 
Vitamin D3                                                  0,0075 mg 
Vitamin E                                                    12 mg 
Vitamin K1                                                  0,0375 mg 
Folic Acid                                                    0,2 mg 
Pantothenic Acid                                         9 mg 
Iron                                                              21 mg 
Magnesium                                                  187,5 mg 
Selenium                                                      0,055 mg 
Zinc                                                              10 mg 
 
Diet progression after bariatric surgery 
1. Liquid Proteic Diet (for 2 weeks)  
Types of food 
Calories/day 
Reduced fat milk Lactose-free: 200ml  
Protein: 52.32g (31.29%) 

Fruit juice: 200ml  
Light white yogurt: 125ml  
Vegetable clear broth: 400ml  
Oral protein supplementation: 400ml 
Fat: 14.52g (19.54%) 
Carbohydrate: 86.6g (51.58%) 
Kcal: 669 
 
2. Pureed Proteic Diet (for 1 week) 
Types of food 
Calories/day 
Reduced fat milk Lactose-free: 200ml  
Light white yogurt: 125ml  
Vegetable clear broth: 400ml  
Oral protein supplementation: 400ml  
Pureed  lean  beef,  chicken  or  turkey,  fish  (or 
baby food meats): 80g 
Pureed fruits (or baby food fruit): 100g  
Soft cheese: 50g 
Extra virgin oil: 10g 
Protein: 62.4g (25.69%) 
Fat: 43.26g (40.07%) 
Carbohydrate: 85.52g (35.21%) 
Kcal: 971.65 
 
3. Soft Solid Proteic Diet (for 2 weeks) 

Types of food 
Calories/day 
Reduced fat milk Lactose-free: 200ml  
Light white yogurt: 125ml  
Oral protein supplementation: 400ml  
Chopped lean  meats (or Lean ground beef or 
turkey, or Deli-sliced turkey, breast, chicken, 
ham): 50g 
Tuna fish,  salmon or white fish: 50g 
Pureed  fruits  (or  baby  food  fruit)  or  canned 
fruits: 100g  
Mashed or well-cooked vegetables: 100g 
Extra virgin oil: 10g 
Protein: 74.4g (30.41%) 
Fat: 32.66g (30.04%) 
Carbohydrate: 99.4g (40.60%) 
Kcal: 978.65 
 
 
 
4. Manteinance (Regular Food) 
Types of food 
Calories/day 

Reduced fat milk Lactose-free: 200ml  
Biscuits: 30g 
Oral protein supplementation: 200ml 
Light white yogurt: 125ml  
Lean red meat (or tender chicken, turkey and 
beef: 70g 
Fish: 70g 
Raw fruits without skins: 100g  
Raw and cooked vegetables: 100g 
Toasted breads or Low fat crackers: 30g  
Extra virgin oil: 20g 
Protein 78.9gm (27.69%) 
Fat 42.24gm (33.35%) 
Carbohydrate: 
116.6 
gm 
(40.9%) 
Kcal 1116.64 
 
Postoperative follow up: 
Total weight loss percent, excess weight loss percent (%EWL), excess BMI loss 
percent,  co-morbidities  control  and  quality  of  life,  evaluated  by  The  TSD-OC 
(SIO obesity-related disability) test (19). It is a questionnaire developed by the 
Italian Society of Obesity (SIO); it is made of 36 items divided into 7 sections: 
pain, rigidity, activities of daily living, housework, outdoor activities, 
occupational activities, and social life. Each question is answered using a visual 

analogue  scale,  with  a  score  ranging  from  0  (absence  of  difficulty)  to  10  (the 
highest degree of disability) for each item. 
Data recording and variables analysis:  
Basic demographic data are recorded as well as detailed information on history, 
preoperative 
data, 
surgical 
procedure, 
intra-operative 
findings, 
and 
postoperative  course.  The  statistical  analysis  will  be  performed  on  the  pooled 
groups. All statistical analyses will be performed using IBM SPSS v.20 
software. P value of less than 0.05 will be considered statistically significant.  
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