Introduction

Wessel’s Rule of Three differentiating ‘fussy’ from ‘content’ babies is still the most used criteria for colic.¹⁴ It says that colic is characterized by paroxysmal, excessive, and inconsolable crying in a healthy and well-fed infant that exceeds 3 hours daily for 3 or more days in a week for a minimum of 3 weeks. The word ‘colic’ comes from ‘kolikos’ (Greek word meaning adjective to ‘kolon’). This suggests that gastrointestinal disturbances had been the prime suspect in infant crying. Increased association of abdominal distension and increased tone with colicky infants points to the fact.

Discussion

Studies by Brazelton et al (1962) and Hunziker (1986) showed that the daily crying time is maximum around 5-6 weeks of age and significantly reduces by 12 weeks of age.^2,5 They also have shown that although colicky infants tend to cry for a longer duration, the numbers of daily crying bouts along with evening clusters as well as the peak age for crying mimic that of non-colicky infants. So there must have some common incidents happening which might have different courses resulting in different outcomes.

Lehtonen (1994) suggested aberrant intestinal flora in the form of inadequate lactobacilli could be playing a role in colic. He presumed that lactobacilli are essential for normal gut mucosal function and their derangement results in aberrant immune functions leading to decreased oral tolerance characterized by an abnormal fatty acid profile of intestine.⁶ However, no strong proof was found but it led researchers to put experimental insights. Works by Adlerberth (2009) and Marques (2010) supports the fact that immediately after birth, the sterile gastrointestinal tract of the newborn gets rapidly colonized by vaginal and intestinal bacteria comprising of facultative anaerobic members like Enterobacteria, Enterococcus, etc.^1,7 Thereafter anaerobic bacteria e.g. Bifidobacterium, Clostridium, and Bacteroides tend to predominate. So there is a period of hand-over which is not non-competitive. Colic probably arises out of these microbial struggles to achieve the final adult-like microbiota.

Breast-fed infants harbor Bifidobacteria in excess compared to bottle-fed infants with Clostridium and Bacteroides sp in abundance.^4,9 Bottle-fed infants usually have more colic episodes. This mandates to understand the mystery of gut microbiome which are mostly non-cultivable. The recent availability of culture-independent and high-throughput techniques has cleared our vision. Roos (2013) found that colicky infants tend to have a decreased fecal bacterial diversity comprising mainly 4 phyla - Proteobacteria, Firmicutes, Actinobacteria, and Bacteroides, compared to non-colic infants.¹⁰ Also, the composition is less stable, and inter-individual variation is frequent (de Weerth, 2013).³ The presence of Enterobacter aerogenes, Pseudomonas, Vibrio, Yersinia, Anaerobiospirillum correlates positively with the environmental variable crying. Different good-quality studies have proven that higher counts of coliforms, especially Klebsiella sp, is strongly associated with the development of colic. These studies also support Lehtonen’s (1994) observation by the finding of reduced Bifidobacteria and Lactobacillus in colicky infants. Savino (2005) pinpointed that Lactobacillus brevis and Lactobacillus lactis are found only in colic cases.¹¹

Probiotic studies also suggest the role of gut microbiota modulation. In a prospective cohort study, 90 breastfed colicky infants were randomly assigned to treatment with Simethicone or Lactobacillus reuteri. Compared to the Simethicone group, the L.reuteri-treated group had significantly reduced crying episodes.¹² This advantage of probiotic supplementation is due to immunological events. Intestinal endogenous flora modulates the Toll-Like Receptors (TLRs) and Nucleotide Oligomerization Domain Receptors (NODRs) over mucosal epithelium. Appropriate interaction results in normal gut motility whereas inappropriate interactions result in neuro-immune and myo-immune abnormalities leading to hyper-reflex enteric neuromusculature response which is perceived as dysmotility or colic. Dysbiosis-induced bacterial components and/or food allergens initiate Th2 cytokines (IL-5, IL-4, IL-13) which in turn act as neurotransmitters and sensitizes the central nervous system. This is acted upon the enteric nervous system resulting in gastrointestinal dysmotility accompanied by persistent visceral hyperalgesia.

We might simply put more insight into this inter-microbial battle in a different way. There is one evolutionary hypothesis ‘Red queen effect’ proposed by Leigh Van Valen which tells that organisms must constantly adapt, evolve, and proliferate not merely to gain a reproductive advantage but also to survive while pitted against ever-evolving opposing organisms in an ever-changing environment. For example, 2 bacterial species X and Y will proliferate equally. For X to be dominant it has to produce substances that inhibit Y e.g. bacteriocins and to overcome it Y has to evolve to have a defense mechanism. Now X needs another counter-defense mechanism while Y must develop a counter-counter-defense strategy to continue. These events lead to disturbances in intestinal mucosal milieu while the hand-over of bacterial species in the newborn’s intestine is considered. That is why these colics are frequent in the first 3 months of life. But what happens thereafter? The intestinal microbiome assumes adult intestinal microbiota structure. Then comes the role of the ‘Black queen hypothesis’. According to Morris et al (2012), this idea is related to the cards game where one needs to have a minimum point to win (‘Moon-shooting’). In terms of microbes, organisms must be dependent on each other to survive better.⁸ This is the basis of the biofilm concept where a diverse group of microbes remain together and have collective survival and proliferative advantages. Acquisition of this Black queen effect results in the mature or adult-type microbiome and colics become rare as organisms now rest in peaceful co-existence. Adults also do get colic when this equilibrium gets disrupted by trauma, dysbiosis, or other factors.