During breath testing, the focus over the last four decades had been the hydrogen level. Now recent data suggest a greater importance of methane as a marker of disease. Methane appears to be a marker of constipation. In a series of studies, it is now clear that methane is associated with clinical constipation as well as a more constipated Bristol Stool Score [22]. Physiologic data suggest that methane gas itself slows intestinal transit [23]. Methane on the breath test also has a proportional relationship with constipation [22, 24–26]. The greater the methane, the more severe the constipation clinically [24].

In the era of the microbiome , methane is interesting in that this gas is produced not by bacteria but by a group of older organisms, the Archaea. Discoveries surrounding methane and the microbiome have allowed the identification of the organism primarily responsible for gastrointestinal methane production. This organism is Methanobrevibacter smithii . Like its byproduct methane, M. smithii levels in the colon appear to be proportional to the degree of constipation [27].

The understanding of this relationship between methane and constipation continues to grow. While older studies suggested that the methanogenic Archaea were relegated to the colon (in particular the left colon), more recent evidence suggests they have a presence in the small intestine as well [28, 29].

Logically, having a greater abundance of microbes in the gut would lead to a greater capacity for gas production. Consistent with this, bloating is one of the most common features of SIBO. This can lead to cramping and abdominal distress or discomfort. Flatulence or belching is also common. Traditionally, changes in bowel function have often been attributed to SIBO. Depending on the cause, these could range from diarrhea to steatorrhea, such as in the case of the blind loop syndrome [6].

More recently, with the growing understanding of the microbiome, methane and the presence of M. smithii are associated with a particular constellation of symptoms. These include bloating, constipation, and even greater body weight [22, 27, 30–35].

It is because of this wide variety of symptoms that bacterial overgrowth may need to be considered in a large number of patients with gastrointestinal complaints.

As mentioned earlier in this chapter, it is important to look at SIBO as an epiphenomenon. There should be a reason for SIBO. Most commonly this is due to a motility problem such as irritable bowel syndrome (IBS) but there are many others (Table 30.2).

The most common disease now associated with SIBO is IBS. This development was initially controversial due to the nature of IBS research at the time. Now there is strong evidence that much of IBS is due to alterations in the intestinal microbiome and SIBO. This thinking formed the basis for a recent approval of rifaximin by the FDA as a treatment of IBS [36]. The mechanism behind the development of SIBO in IBS is still being explored. However, data suggest that the SIBO could be linked to an initial exposure to acute gastroenteritis [37]. In a validated animal model, infection with Campylobacter jejuni , one of the most common causes of acute gastroenteritis [38, 39], precipitates the development of IBS-like symptoms which correlate with the development of SIBO [40, 41]. Newer data demonstrate that this is through the development of autoimmunity to the cytoskeletal protein vinculin which could impair enteric neuromuscular function and anatomy leading to stasis [42]. These anti-CdtB and anti-vinculin antibodies are now being used in a diagnostic test for post-infectious IBS [43]. If these data continue to hold, a subset of IBS is essentially an autoimmune condition resulting from gastroenteritis and subsequent gut neuropathy leading to SIBO.

In addition, new revelations in the study of IBS identified a link between methane and constipation-predominant IBS [22, 24–26]. It is now known that nearly all patients with methane on breath test (“methane overgrowth”) have constipation as a phenotype.

Although there is a great deal of excitement around these developments in IBS, traditional associations between SIBO and motility disorders still hold. For example, patients with pseudo-obstruction can have SIBO due to the ileus pattern. Recall that SIBO can be caused by any reduction in bowel flow. The same is true for gastroparesis. While in gastroparesis the emphasis is poor flow through the stomach, the motor disturbances are not defined by a line of normalcy past the pylorus. The dysfunction often extends into the small bowel leading to SIBO.

As already discussed briefly, mechanical impairments to the flow of small bowel contents will lead to SIBO. The most common of these are intestinal adhesions secondary to previous surgery [1, 3, 44]. While tradition describes blind loops and antrectomy as a common cause of SIBO, these are now rare. Few people have antrectomy for refractory peptic ulcers these days and blind loop syndrome is more uncommon. While bariatric surgery such as Roux-en-Y gastric bypass alters anatomy, the intestinal flow rate is often higher than normal leading to less SIBO compared to older techniques [1].

Metabolic causes of SIBO are also common. Diabetes has a dual effect on the development of SIBO. It is theoretically possible that hyperglycemia is a risk, yet acute hyperglycemia itself (not necessarily chronic) can have profound inhibiting effects on intestinal motility [45–48]. As diabetes is very common, this may be a common cause of chronic intestinal symptoms in diabetic subjects.

More obvious is the association between achlorhydria and bacterial overgrowth [2, 3, 49]. In this case, the lack of gastric acid leads to easier colonization of the upper intestinal tract by bacteria. Often in this case, the colonization is due to oral flora (less gram negative bacteria). This is also true for the iatrogenic causes of low acid such as use of proton pump inhibitors [3, 50]. However, this may be more complicated as reduced acid reduces the protons needed to fuel methane production. In one study, the use of proton pump inhibitors was associated with a lower prevalence of methane on breath testing [51].

A number of disorders of immune function are also associated with SIBO. Conditions that reduce immunity of the gut such as IgA deficiency and combined variable immunodeficiency can reduce the response to gut microbes leading to SIBO [6, 52, 53]. Advance HIV and its effect on immune function has also been an important cause of SIBO in the past. Better treatments of HIV have made this less common now.

In addition to diseases of reduced immune function, autoimmune disease has been associated with SIBO as well although the mechanisms by which this occurs are less clear. In the case of scleroderma, the changes in gut motor function (neuropathy) are an obvious cause of SIBO [6, 54]. However, lupus and fibromyalgia [55] are less well understood.

Finally, medications can have an impact on the development of SIBO. Acid-reducing drugs have already been discussed. Yet, the greatest impact may be opiate agonists. In studies from the 1990s it was demonstrated that even a short course of opiate agonists could lead to SIBO even in healthy volunteers [56]. With growing reports of opiate prescription and overuse, this could be an important cause of SIBO.

Management of SIBO comprises three goals: (i) controlling disease flares (induction of remission); (ii) decreasing the chance of recurrence after induction of remission (maintenance of remission); and (iii) identifying and addressing the modifiable underlying cause(s) [1].