Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.

We studied the anorectal manometric and urodynamic pattern of seven patients who had right and/or left frontal lobe injury to investigate the possibility that the frontal lobe area plays an important role in control of anorectal motility as it does for the urinary bladder. We found that the disturbances of anorectal manometric recordings were similar to those of urodynamic recordings: (1) lack of urinary bladder filling sensation (two cases), increased perception threshold of rectal distension (two cases); (2) uninhibited detrusor contractions during filling (five cases), spontaneous rectal contractions during the resting step (four cases); (3) absence of micturition (one case), absence of rectoanal inhibitory reflex (one case). Furthermore, in all but one patient, we observed a decrease in the amplitude and duration of the voluntary contraction of the anal canal (six cases). However, in two of the seven patients we found hypertonia in the anal canal (upper part: one case, lower part: one case), but never in the urethral canal. Our results suggest that frontal lobe may be involved in the nervous control of anorectal motility as it is for urinary bladder function. However, the lack of correlation between urinary and anorectal anomalies in individual cases suggests that these functions depend on distinct areas of the frontal lobe.

The present study revealed the site of origin and the possible function of a supraspinal descending-inhibitory influence over the lumbar sympathetic component of the recto-rectal reflex of guinea pigs. The recto-rectal reflex contraction was not changed by suprapontine transection. It completely disappeared after subpontine transection, but returned immediately after additional section of the colonic nerves, which contain the sympathetic inhibitory outflow to the rectum, i.e., subpontine transection with the lumbar colonic nerves transected did not suppress the recto-rectal reflex. These results indicate that a descending pathway which can inhibit the lumbar sympathetic component of the reflex may originate in the pons. On stimulation at sites within the pons of animals which had been spinalized at L4 we were able to evoke an increase of rectal motility and an inhibition of the lumbar colonic efferent discharges, thus producing a response which is comparable to the reflex response produced by afferent stimulation of the rectum. The sites from which this effect could be evoked were mainly located in a band running rostrocaudally through the lateral reticular formation of the rostral part of the pons, medial to the sensory nucleus of the trigeminal nerve.

The role of pontine reticula units (PRU) responding to afferent impulses from the distal colon and anal mucosa was studied in dogs. The 465 PRU were classified into 4 groups on the basis of the pattern of discharge in response to afferent stimulation (AS) of rectal branches (RB) of the pelvic nerve: Group I (G-I) responded with a short burst (latency, 36 +/- 16 msec); G-II responded with an early short burst (latency, 41 +/- 21 msec), followed by a late long-lasting train of spikes (latency, 187 +/- 110 msec); and G-III responded with a long-lasting train of spikes (latency, 189 +/- 130 msec). G-IV had spontaneous discharges which were temporally inhibited by AS. G-II and G-III PRU showed remarkable facilitation similar to that of the long latency reflex discharges of RB. G-I PRU showed habituation. Most of G-II and G-III PRU discharged simultaneously with the reflex discharges of RB; these cause the contractions of defecation in the distal colon. In each group, 6.4 +/- 14.8% of PRU were reticulospinal units with descending axons running beyond the 1st lumbar segment of the spinal cord. It was concluded that the pontine defecation reflex center plays an essential role in defecating activity.

In the guinea pig, defecation is controlled by the myenteric plexus, whose activity is modulated by the sacral spinal and supraspinal centers. The purpose of this study is to clarify the control of defecation reflex by sympathetic nerves. The propulsive contractions of the rectum produced by rectal distension (recto-rectal excitatory reflex response) were abolished after transection of the Th 13 and/or L 4 segment. This response was reproduced again after removal of the lumbar segments (L1--4), division of the lumbar dorsal roots (L1--4), the lumbar splanchnic nerves or lumbar colonic nerves (LCN). The frequency of efferent discharges of LCN was increased slightly by rectal distension and remarkably increased after Th 13 and/or L 4 transection. Thus, there occurs during the recto-rectal reflex not only mucosal intrinsic reflex and sacral excitatory reflex via the pelvic nerves but also a lumbar inhibitory reflex via the colonic nerves, whose center may be located in the upper lumbar segments. But, the activity of the inhibitory center was depressed by the supraspinal center, so that an excitatory reflex is produced more dominantly than an inhibitory one in normal animals. All these extrinsic reflexes coordinate the activity of the myenteric plexus in defecation reflex.