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Arvola (2006)
16
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Forty infants with rectal bleeding (mean age = 2.7 months), 68% fully breastfeed. |
FISH |
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Tampere, Finland
|
Colonoscopy and biopsy (n=39): 84% focal erythema and/or ulceration. Inflammation in 59% and eosinophilic infiltration in 23%. |
↓Bifidobacterias; ↓Lactobacilos/Enterrococcus; ≈ Clostridium; ≈ Bacteroides; ↓Total microbial count |
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Cow milk elimination diet was prescribed randomly for 19 infants, while 21 remained with the same diet. Rectal bleeding resolved in approximately 5 days in all the infants, independently of diet type. |
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Open oral food challenge was positive only in 5/7 infants. According to the authors, CMA was diagnosed in only 7 (18%) infants. |
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Sixty-four healthy infants (mean age = 3.6 months) as control group. |
|
|
Thompson-
Chagoyan (2010 and 2011)
8
,
9
|
Forty-six infants aged 2-12 months (median = 6 months) were diagnosed with IgE-mediated CMA. |
FISH |
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Granada, Spain
|
Clear history of immediate hypersensitivity, positive skin-prick test, specific IgE to any of the cow milk protein, and positive challenge test. |
Thompson-Chagoyan et al., 2010; ↑Anaerobic bactéria; ≈ Aerobic bacteria; ≈ Enterobacteria; ≈ Lactobacilli; ≈ Bifidobacteria; ≈ Clostridia; ↓Yeast; ↑Total microbial count; Thompson-Chagoyan et al., 2011: ≈ Bifidobacterium genus; ↑Clostridium coccoides; ↑Atopobium cluster; ≈ C. leptum group; ≈ Bacteroides group; ≈ Enterobacteria group; ≈ Lactobacillus group; ≈ Streptococcus group; ≈ C. perfringens + C. difficile; ↑Total microbial count |
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Forty-six healthy (non-allergic) infants age-matched as a control group. |
FISH |
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Francavilla R et al., 2012
10
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Sixteen infants with IgE-mediated CMA (median age = 7.5 months); |
↓Bifidobacterias↑ ↑Bacteroides ↑Clostridium
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Bari, Italy
|
Twelve healthy controls (median age = 6.9 months); |
|
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Kumagai H et al., 2012
11
|
Fifteen infants with blood-streaked stools (median age = 3 months); |
PCR amplification of the 16S rRNA gene |
|
Morioka, Japão
|
Fifteen healthy controls (median age = 3 months); |
↓ counts of obligate anaerobes; ↓C. leptum ↓ Bacteroides fragilis ↓ Prevotella ↓ Clostridium and Bacteroides ↓ E. coli ↑Klebsiella ↓ C. coccoides ≈ Bifidobacterium ≈ Atopobium
|
|
Berni-Canani (2016)
12
|
Nineteen infants with IgE-mediated CMA still receiving cow milk protein at age 1-12 months (mean = 4 months in an EHF group and mean = 4.3 months in an EHF + LGG group). |
16S rDNA sequencing using the Illumina MiSeq platform |
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Naples, Italy
|
Diagnosis of IgE-mediated CMA based on clinical history, DBPCFC, and serum-specific anti-cow milk protein IgE. |
↑ Shannon diversity and Pielou’s evenness ≈ abundance ↓ Bifidobacteriaceae ↓ Streptococcaceae ↓ Enterobacteriaceae (↓ Escherichia) ↓ Enterococcaceae ↑Ruminococcaceae ↑ Lachnospiraceae 73% Bacteroidetes and Firmicutes taxa ↑Ruminococcus genus ↑Faecalibacterium genus ↓ Bifidobacterium ↓ Escherichia
|
| |
Twenty healthy controls (mean age = 4.2 months) |
|
|
Berni-Canani (2018)
18
|
Twenty-three infants (mean age = 11.4 months) with non-IgE-mediated CMA still receiving standard formula. |
V3-V4 region of the 16S rRNA sequencing using the Illumina platform |
|
Naples, Italy
|
Diagnosis of non-IgE-mediated CMA based on clinical history, negative result of skin prick test, and/or negative level of IgE serum-specific anti-cow milk proteins, and a DBPCFC. Twenty-three infants (mean age = 12.9 months) with negative clinical history for any allergic condition (consultations for evaluation of minimal surgical procedures or vaccination programs). |
≈ Shannon diversity; Phyla and genera in parentheses: ↑Bacteroidetes (↑Bacteroides and ↑Alistipes) ≈ Firmicutes (↑Sarcina, ≈Lactobacillus, and ≈Clostridium) ≈ Proteobacteria ≈ Verrucomicrobia ≈ Actinobacteria (≈Bifidobacteria) |
|
Dong (2018)
25
|
Sixty infants ≤4 months of age (mean = 2.9 months) with challenge-proven non-IgE- or IgE-mediated CMA |
16S rRNA gene sequencing using the Illumina platform |
|
Shanghai, China
|
Clinical and laboratorial data followed by positive double-blind placebo-controlled challenge. |
↓ Shannon diversity; ↓ Total microbiota ≈ Actinobacteria (≈ Bifidobacteriacea) ↓ Bacteroidetes (↓ Bacteroidaceae) ↓ Bacteroides genus ≈ Firmicutes (Lactobacillaceae; Veillonellaceae; Lachnospiraceae; Ruminococcaceae; and ≈ class Clostridia) ↑Proteobacteria (≈Alcaligenaceae; ↑Enterobacteriaceae) ↑Enterobacteriacea/Bacteroidaceae;
|
| |
Sixty healthy age-matched infants exclusively breast fed until introduced to milk formulae at the same age as paired CMA infants |
|
|
Aparicio (2020)
22
|
Eleven infants (age ≤6 months) with non-IgE mediated CMA; 4 with regurgitation, vomiting, refusal of food, constipation, perianal erythema, and improvement with cow milk protein exclusion diet; and 3 with proctocolitis in exclusive breast feeding (no dietary intervention in the mother) and negative stool microbiological study. |
16S rDNA gene using the Illumina platform |
|
Madrid, Spain
|
No mention of oral challenge test |
≈ Richness and Shannon index; Beta diversity did not reveal distinct microbial profile. |
| |
Eight healthy controls (age ≤4 months), 7 born via vaginal delivery, and no mention of feeding type. |
↓ Bifidobacterium ≈ Collinsella ≈ Bacteroides ≈ Enterococcus ≈ Lactobacillus ≈ Streptococcus ↓ Erysipelatoclostridium ≈ Veillonella ≈ Escherichia_Shigella ≈ Klebsiella ≈ Unclassified_Enterobacteriaceae ↑Lachnospiraceae ↑Eggerthellaceae ↑Peptostreptococcaceae
|
|
Mennini (2021)
13
|
Fourteen infants aged 10-15 months (mean age = 12.9 months) with IgE-mediated CMA. |
16S rRNA gene sequencing using THE Illumina platform and qRT-PCR |
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Rome, Italy
|
Twelve infants (mean age = 12.6 months) sensitized but tolerant to cow milk protein. |
≈ Alpha-diversity (Observed, Chao1 and Shannon indexes) ≠ Beta-diversity (CMA group was clearly separated from others) |
| |
Diagnosis of CMA: DBPCFC |
↓ Phylum Verrocomicrobia ↑Phylum Firmicutes (Sensibilization > healthy) ↑Genera Pasteurellaceae; ↑Genera Actinobacillus ↑Genera Haemophilus ↑Genera Erwinia ↑Genera Klebsiella ↑Prevotella ↓ Parabacteroides ↓ Genera Granulicatella ↑Genera Streptococcus ↓ Genera Anaerotruncus ↓ Genera Ruminococcaceae_g_ ≈ B. breve, ≈ B. longum subsp. Longum, ≈ B. longum subsp. infantis
|
| |
Definition of sensitization: positive skin prick test and/or allergen-specific IgE. |
|
| |
Fourteen heathy controls infants (mean age = 12,6 months) |
|
|
Martin et al. (2022)
23
|
Eighty-one infants (mean age = 1 month) from a sample of 954 (81/954) with followed since birth; they presented with suspected FPIAP during longitudinal follow-up. |
16S rRNA gene sequencing using the Illumina platform |
|
Boston Metropolitan area, USA
|
Each physician’s clinical diagnosis of FPIAP was based on guaiac positive or grossly bloody stool not attributable to another etiology. Treatment of FPIAP was per clinician discretion. Therefore, reintroduction of the suspected offending food to confirm diagnosis was not routinely done, and the order of foods eliminated was not standardized. Information concerning symptoms resolution was collected retrospectively based on chart review. |
Pre-symptomatic ≈ alpha-diversity (Chao1), except at 4 months (↑richness in symptomatic group) ≈ stability (Bray-Curtis) |
| |
Some infants received Lactobacillus-containing probiotics. |
0 to 2 months ↑Genera Enterobacteriaceae (most likely, Escherichia) ↓ Family Clostridiaceae ↓ Unknown family Clostridiales ↓ Lactobacillus Last pre-symptomatic sample ↑Genera Enterobacteriaceae
|
| |
Seventy-nine healthy infants were paired according to type of delivery and feeding and previous use of antibiotic. |
First symptomatic sample and symptomatic ↑Enterobacteriaceae genus ↓ family Clostridiales; Symptomatic ≈ alpha-diversity: Chao1 richness index ↓ Clostridiales ↑Genera Enterobacteriaceae (most likely, Escherichia)
|
|
Wurm (2023)
24
|
Fourteen infants (mean age = 11.1 weeks) with suspected FPIAP. All recovered with an elimination diet. |
16S rRNA sequencing using the Illumina platform |
|
Graz, Austria
|
Positive oral challenge test in 2 infants. |
≈ Alpha diversity index (richness, phylogeny, and Shannon uniformity) ≠ Beta-diversity: suspected FPIAP group was clearly separated from healthy controls (Bray-Curtis index and weighted UniFrac) |
| |
Fifty-five healthy control infants (mean age = 12.7 weeks) |
↓ Genus Bifidobacterium ↓ Bifidobacterium spp ↓ Bifidobacterium longum ↑Clostridium sensu stricto 1 ↑Clostridium butyricum
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